Target Information

Target General Information

Top

Target ID

T68547 (Former ID: TTDS00095)

Target Name

Histone deacetylase 1 (HDAC1)

Synonyms

RPD3L1; HD1

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Gene Name

HDAC1

Target Type

Successful target

[1]

Disease

[+] 2 Target-related Diseases

Multiple myeloma [ICD-11: 2A83]

Mycosis fungoides [ICD-11: 2B01]

Function

Gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events. Histone deacetylases act via the formation of large multiprotein complexes. Deacetylates SP proteins, SP1 and SP3, and regulates their function. Component of the BRG1-RB1-HDAC1 complex, which negatively regulates the CREST-mediated transcription in resting neurons. Upon calcium stimulation, HDAC1 is released from the complex and CREBBP is recruited, which facilitates transcriptional activation. Deacetylates TSHZ3 and regulates its transcriptional repressor activity. Deacetylates 'Lys-310' in RELA and thereby inhibits the transcriptional activity of NF-kappa-B. Deacetylates NR1D2 and abrogates the effect of KAT5-mediated relieving of NR1D2 transcription repression activity. Component of a RCOR/GFI/KDM1A/HDAC complex that suppresses, via histone deacetylase (HDAC) recruitment, a number of genes implicated in multilineage blood cell development. Involved in CIART-mediated transcriptional repression of the circadian transcriptional activator: CLOCK-ARNTL/BMAL1 heterodimer. Required for the transcriptional repression of circadian target genes, such as PER1, mediated by the large PER complex or CRY1 through histone deacetylation. Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4).

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BioChemical Class

Carbon-nitrogen hydrolase

UniProt ID

HDAC1_HUMAN

EC Number

EC 3.5.1.98

Sequence

MAQTQGTRRKVCYYYDGDVGNYYYGQGHPMKPHRIRMTHNLLLNYGLYRKMEIYRPHKAN
AEEMTKYHSDDYIKFLRSIRPDNMSEYSKQMQRFNVGEDCPVFDGLFEFCQLSTGGSVAS
AVKLNKQQTDIAVNWAGGLHHAKKSEASGFCYVNDIVLAILELLKYHQRVLYIDIDIHHG
DGVEEAFYTTDRVMTVSFHKYGEYFPGTGDLRDIGAGKGKYYAVNYPLRDGIDDESYEAI
FKPVMSKVMEMFQPSAVVLQCGSDSLSGDRLGCFNLTIKGHAKCVEFVKSFNLPMLMLGG
GGYTIRNVARCWTYETAVALDTEIPNELPYNDYFEYFGPDFKLHISPSNMTNQNTNEYLE
KIKQRLFENLRMLPHAPGVQMQAIPEDAIPEESGDEDEDDPDKRISICSSDKRIACEEEF
SDSEEEGEGGRKNSSNFKKAKRVKTEDEKEKDPEEKKEVTEEEKTKEEKPEAKGVKEEVK
LA

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3D Structure

Click to Show 3D Structure of This Target

PDB

HIT2.0 ID

T42D4V

Drugs and Modes of Action

Top

Approved Drug(s)

[+] 4 Approved Drugs

Panobinostat

Drug Info

Approved

Multiple myeloma

[2]

Romidepsin

Drug Info

Approved

Cutaneous T-cell lymphoma

[3], [4]

Vorinostat

Drug Info

Approved

Cutaneous T-cell lymphoma

[5], [6]

HBI-8000

Drug Info

Registered

Solid tumour/cancer

[7], [8]

Clinical Trial Drug(s)

[+] 11 Clinical Trial Drugs

ITF2357

Drug Info

Phase 3

Duchenne dystrophy

[9]

NVP-LAQ824

Drug Info

Phase 3

Mood disorder

[10]

SNDX-275

Drug Info

Phase 3

Breast cancer

[11]

MGCD-0103

Drug Info

Phase 2

Solid tumour/cancer

[13], [14]

Phenylbutyrate

Drug Info

Phase 2

Urea cycle disorder

[15], [16]

Resminostat

Drug Info

Phase 2

Hepatocellular carcinoma

[17], [18]

Sodium butyrate

Drug Info

Phase 2

Refractory sickle cell ulcers

[19]

CHR-3996

Drug Info

Phase 1/2

Lymphoma

[20]

OBP-801

Drug Info

Phase 1

Solid tumour/cancer

[21]

RG-2833

Drug Info

Phase 1

Friedreich's ataxia

[22], [23]

SB-639

Drug Info

Phase 1

Solid tumour/cancer

[24]

Discontinued Drug(s)

[+] 3 Discontinued Drugs

AN-9

Drug Info

Discontinued in Phase 2

Melanoma

[27]

Pyroxamide

Drug Info

Discontinued in Phase 1

Solid tumour/cancer

[28]

Oxamflatin

Drug Info

Terminated

Solid tumour/cancer

[35]

Preclinical Drug(s)

[+] 5 Preclinical Drugs

4SC-202

Drug Info

Preclinical

Solid tumour/cancer

[18]

HC-Toxin

Drug Info

Preclinical

Solid tumour/cancer

[32]

M-carboxycinnamic acid bishydroxamide

Drug Info

Preclinical

Solid tumour/cancer

[33]

Scriptaid

Drug Info

Preclinical

Solid tumour/cancer

[16], [34]

SK-7068

Drug Info

Preclinical

Solid tumour/cancer

[31]

Mode of Action

[+] 2 Modes of Action

Inhibitor

[+] 221 Inhibitor drugs

Panobinostat

Drug Info

[1], [36], [37], [38]

Romidepsin

Drug Info

[4]

Vorinostat

Drug Info

[1], [39], [38]

ITF2357

Drug Info

[41], [6]

NVP-LAQ824

Drug Info

[42]

SNDX-275

Drug Info

[6]

MGCD-0103

Drug Info

[1], [37], [38]

Phenylbutyrate

Drug Info

[16]

Resminostat

Drug Info

[18]

Sodium butyrate

Drug Info

[38], [43]

CHR-3996

Drug Info

[44]

OBP-801

Drug Info

[45]

SB-639

Drug Info

[37]

Diaryl amine derivative 2

Drug Info

[46]

Diaryl amine derivative 3

Drug Info

[46]

Isosteric imidazolyl pyrimidine derivative 1

Drug Info

[47]

PMID28092474-Compound-32a

Drug Info

[46]

PMID28092474-Compound-32b

Drug Info

[46]

PMID28092474-Compound-32c

Drug Info

[46]

PMID28092474-Compound-32d

Drug Info

[46]

PMID28092474-Compound-32e

Drug Info

[46]

PMID28092474-Compound-32f

Drug Info

[46]

PMID28092474-Compound-32g

Drug Info

[46]

PMID28092474-Compound-32h

Drug Info

[46]

PMID28092474-Compound-32i

Drug Info

[46]

PMID28092474-Compound-32j

Drug Info

[46]

PMID28092474-Compound-32k

Drug Info

[46]

PMID28092474-Compound-32m

Drug Info

[46]

PMID28092474-Compound-32n

Drug Info

[46]

PMID28092474-Compound-32o

Drug Info

[46]

PMID28092474-Compound-32p

Drug Info

[46]

PMID28092474-Compound-32q

Drug Info

[46]

PMID28092474-Compound-32r

Drug Info

[46]

PMID28092474-Compound-32t

Drug Info

[46]

PMID28092474-Compound-32u

Drug Info

[46]

PMID28092474-Compound-32v

Drug Info

[46]

PMID28092474-Compound-32x

Drug Info

[46]

PMID28092474-Compound-32y

Drug Info

[46]

PMID28092474-Compound-32z

Drug Info

[46]

PMID28092474-Compound-33a

Drug Info

[46]

PMID28092474-Compound-33b

Drug Info

[46]

PMID28092474-Compound-33c

Drug Info

[46]

PMID28092474-Compound-33d

Drug Info

[46]

PMID28092474-Compound-33e

Drug Info

[46]

PMID28092474-Compound-33f

Drug Info

[46]

PMID28092474-Compound-33g

Drug Info

[46]

PMID28092474-Compound-33h

Drug Info

[46]

PMID28092474-Compound-33i

Drug Info

[46]

PMID28092474-Compound-33j

Drug Info

[46]

PMID28092474-Compound-33k

Drug Info

[46]

PMID28092474-Compound-33l

Drug Info

[46]

PMID28092474-Compound-33m

Drug Info

[46]

PMID28092474-Compound-33o

Drug Info

[46]

PMID28092474-Compound-33p

Drug Info

[46]

PMID28092474-Compound-34a

Drug Info

[46]

PMID28092474-Compound-34b

Drug Info

[46]

PMID28092474-Compound-34c

Drug Info

[46]

PMID29671355-Compound-11

Drug Info

[48]

PMID29671355-Compound-18

Drug Info

[48]

PMID29671355-Compound-19

Drug Info

[48]

PMID29671355-Compound-21

Drug Info

[48]

PMID29671355-Compound-22

Drug Info

[48]

PMID29671355-Compound-23

Drug Info

[48]

PMID29671355-Compound-24

Drug Info

[48]

PMID29671355-Compound-25

Drug Info

[48]

PMID29671355-Compound-26

Drug Info

[48]

PMID29671355-Compound-31

Drug Info

[48]

PMID29671355-Compound-38a

Drug Info

[48]

PMID29671355-Compound-39

Drug Info

[48]

PMID29671355-Compound-43

Drug Info

[48]

PMID29671355-Compound-44

Drug Info

[48]

PMID29671355-Compound-55

Drug Info

[48]

PMID29671355-Compound-56

Drug Info

[48]

PMID29671355-Compound-59

Drug Info

[48]

PMID29671355-Compound-61

Drug Info

[48]

PMID29671355-Compound-62

Drug Info

[48]

PMID29671355-Compound-65a

Drug Info

[48]

PMID29671355-Compound-67

Drug Info

[48]

PMID29671355-Compound-73

Drug Info

[48]

PMID29671355-Compound-8

Drug Info

[48]

PMID29671355-Compound-9

Drug Info

[48]

AN-9

Drug Info

[38]

Pyroxamide

Drug Info

[37], [38]

4SC-202

Drug Info

[18]

HC-Toxin

Drug Info

[37]

M-carboxycinnamic acid bishydroxamide

Drug Info

[37], [38]

Scriptaid

Drug Info

[37], [16], [38]

SK-7068

Drug Info

[37], [38]

Oxamflatin

Drug Info

[37], [38]

(E)-8-Biphenyl-4-yl-1-oxazol-2-yl-oct-7-en-1-one

Drug Info

[49]

1,1,1-Trifluoro-8-(4-phenoxy-phenoxy)-octan-2-one

Drug Info

[50]

1,1,1-Trifluoro-8-phenoxy-octan-2-one

Drug Info

[50]

2-(methylsulfonylthio)ethyl 2-propylpentanoate

Drug Info

[51]

4-Benzenesulfonylamino-N-hydroxy-benzamide

Drug Info

[52]

4-Benzoylamino-N-hydroxy-benzamide

Drug Info

[53]

4-Butyrylamino-N-hydroxy-benzamide

Drug Info

[54]

4-Chloro-N-(5-hydroxycarbamoyl-pentyl)-benzamide

Drug Info

[55]

4-Dimethylamino-N-(6-mercapto-hexyl)-benzamide

Drug Info

[56]

4-Hydroxy-N-(5-hydroxycarbamoyl-pentyl)-benzamide

Drug Info

[57]

100

4-Phenylbutyrohydroxamic acid

Drug Info

[58]

101

4-tert-butyl-N-hydroxybenzamide

Drug Info

[59]

102

5-(4-hydroxyphenyl)-3H-1,2-dithiole-3-thione

Drug Info

[51]

103

5-Mercapto-pentanoic acid phenylamide

Drug Info

[56]

104

6-(2-Bromo-acetylamino)-hexanoic acid phenylamide

Drug Info

[56]

105

6-(3-Benzoyl-ureido)-hexanoic acid hydroxyamide

Drug Info

[60]

106

6-(9H-carbazol-9-yl)-N-hydroxyhexanamide

Drug Info

[61]

107

6-benzenesulfinylhexanoic acid hydroxamide

Drug Info

[62]

108

6-benzenesulfonylhexanoic acid hydroxamide

Drug Info

[62]

109

6-Mercapto-hexanoic acid phenylamide

Drug Info

[56]

110

6-Phenoxy-hexane-1-thiol

Drug Info

[56]

111

6-phenylsulfanylhexanoic acid hydroxamide

Drug Info

[62]

112

7-(1H-indol-5-yloxy)-N-hydroxyheptanamide

Drug Info

[63]

113

7-(3-Benzoyl-ureido)-heptanoic acid hydroxyamide

Drug Info

[60]

114

7-(4-(dimethylamino)phenoxy)-N-hydroxyheptanamide

Drug Info

[63]

115

7-(Biphenyl-3-yloxy)-1-oxazol-2-yl-heptan-1-one

Drug Info

[49]

116

7-(Biphenyl-4-yloxy)-1-oxazol-2-yl-heptan-1-one

Drug Info

[49]

117

7-(Biphenyl-4-yloxy)-heptanoic acid hydroxyamide

Drug Info

[64]

118

7-(Naphthalen-2-yloxy)-1-oxazol-2-yl-heptan-1-one

Drug Info

[49]

119

7-Biphenyl-4-yl-heptanoic acid hydroxyamide

Drug Info

[65]

120

7-Mercapto-heptanoic acid biphenyl-3-ylamide

Drug Info

[56]

121

7-Mercapto-heptanoic acid biphenyl-4-ylamide

Drug Info

[56]

122

7-Mercapto-heptanoic acid phenylamide

Drug Info

[56]

123

7-Mercapto-heptanoic acid pyridin-3-ylamide

Drug Info

[56]

124

7-Mercapto-heptanoic acid quinolin-3-ylamide

Drug Info

[56]

125

7-mercapto-N-(4-phenylthiazol-2-yl)heptanamide

Drug Info

[66]

126

7-Phenoxy-heptanoic acid hydroxyamide

Drug Info

[65]

127

8-(3-Benzoyl-ureido)-octanoic acid hydroxyamide

Drug Info

[60]

128

8-(4-bromophenyl)-N-hydroxy-8-oxooctanamide

Drug Info

[67]

129

8-(Biphenyl-3-yloxy)-1,1,1-trifluoro-octan-2-one

Drug Info

[50]

130

8-(biphenyl-4-yl)-N-hydroxy-8-oxooctanamide

Drug Info

[67]

131

8-(Biphenyl-4-yloxy)-1,1,1-trifluoro-octan-2-one

Drug Info

[50]

132

8-(Biphenyl-4-yloxy)-2-oxo-octanoic acid

Drug Info

[64]

133

8-Oxo-8-phenyl-octanoic acid

Drug Info

[57]

134

8-Oxo-8-phenyl-octanoic acid hydroxyamide

Drug Info

[55]

135

8-Phenyl-octanoic acid hydroxyamide

Drug Info

[65]

136

9,9,9-Trifluoro-8-oxo-nonanoic acid phenylamide

Drug Info

[50]

137

9-(Biphenyl-4-yloxy)-1,1,1-trifluoro-nonan-2-one

Drug Info

[50]

138

ADS-100380

Drug Info

[68]

139

ADS-102550

Drug Info

[68]

140

Azithromycin-N-benzyltriazolyldecahydroxamic Acid

Drug Info

[69]

141

Azithromycin-N-benzyltriazolylhexahydroxamic Acid

Drug Info

[69]

142

Azithromycin-N-benzyltriazolylnonahydroxamic Acid

Drug Info

[69]

143

Azithromycin-N-benzyltriazolyloctahydroxamic Acid

Drug Info

[69]

144

Azithromycinarylalkylhydroxamic Acid

Drug Info

[69]

145

AZUMAMIDE B

Drug Info

[70]

146

AZUMAMIDE C

Drug Info

[70]

147

AZUMAMIDE E

Drug Info

[70]

148

Cyclo(-L-Am7(S2Py)-A2in-L-Ala-D-Pro-)

Drug Info

[71]

149

Cyclo(-L-Am7(S2Py)-Aib-L-Ala-D-Pro-)

Drug Info

[71]

150

Cyclo(-L-Am7(S2Py)-Aib-L-Ala-D-Tic-)

Drug Info

[71]

151

Cyclo(-L-Am7(S2Py)-Aib-L-Ph5-D-Pro-)

Drug Info

[71]

152

Cyclo(-L-Am7(S2Py)-Aib-L-Phg-D-Pro-)

Drug Info

[71]

153

Cyclo(-L-Am7(S2Py)-Aib-L-Ser(Bzl)-D-Pro-)

Drug Info

[71]

154

Cyclo(-L-Am7(S2Py)-Aib-L-Ser-D-Pro-)

Drug Info

[71]

155

Cyclo(-L-Am7(S2Py)-D-2MePhe-L-Ala-D-Pro-)

Drug Info

[71]

156

Cyclo(-L-Am7(S2Py)-D-A1in-L-Ala-D-Pro-)

Drug Info

[71]

157

Cyclo(-L-Am7(S2Py)-L-A1in-L-Ala-D-Pro-)

Drug Info

[71]

158

Cyclostellettamine derivative

Drug Info

[72]

159

Desclasinose Azithromycinarylalkyl Hydroxamate

Drug Info

[69]

160

Gymnochrome E

Drug Info

[73]

161

N,8-dihydroxy-8-(naphthalen-2-yl)octanamide

Drug Info

[67]

162

N-(2,3-Dimethylphenyl)-N'-hydroxyoctanediamide

Drug Info

[74]

163

N-(2,4-Dimethylphenyl)-N'-hydroxyoctanediamide

Drug Info

[74]

164

N-(2,5-Dimethylphenyl)-N'-hydroxyoctanediamide

Drug Info

[74]

165

N-(2,6-Dimethylphenyl)-N'-hydroxyoctanediamide

Drug Info

[74]

166

N-(2-amino-5-(thiophen-2-yl)phenyl)nicotinamide

Drug Info

[75]

167

N-(2-aminophenyl)-4-(chroman-3-ylmethyl)benzamide

Drug Info

[76]

168

N-(2-aminophenyl)nicotinamide

Drug Info

[75]

169

N-(2-aminophenyl)quinoxaline-6-carboxamide

Drug Info

[77]

170

N-(2-Ethylphenyl)-N'-hydroxyoctanediamide

Drug Info

[74]

171

N-(2-Mercapto-ethyl)-N'-phenyl-oxalamide

Drug Info

[78]

172

N-(2-Mercapto-ethyl)-N'-phenyl-succinamide

Drug Info

[78]

173

N-(3,4-Dimethylphenyl)-N'-hydroxyoctanediamide

Drug Info

[74]

174

N-(3,5-Dimethylphenyl)-N'-hydroxyoctanediamide

Drug Info

[74]

175

N-(3-Ethylphenyl)-N'-hydroxyoctanediamide

Drug Info

[74]

176

N-(4-aminobiphenyl-3-yl)nicotinamide

Drug Info

[75]

177

N-(4-Ethylphenyl)-N'-hydroxyoctanediamide

Drug Info

[74]

178

N-(4-hydroxybiphenyl-3-yl)benzamide

Drug Info

[75]

179

N-(5-Hydroxycarbamoyl-pentyl)-4-nitro-benzamide

Drug Info

[55]

180

N-(6-Mercapto-hexyl)-benzamide

Drug Info

[56]

181

N-hydroxy-2,2'-bithiophene-5-carboxamide

Drug Info

[68]

182

N-Hydroxy-4-((R)-2-phenyl-butyrylamino)-benzamide

Drug Info

[53]

183

N-Hydroxy-4-((S)-2-phenyl-butyrylamino)-benzamide

Drug Info

[53]

184

N-Hydroxy-4-(2-phenyl-butyrylamino)-benzamide

Drug Info

[53]

185

N-Hydroxy-4-(3-phenyl-propionylamino)-benzamide

Drug Info

[79]

186

N-Hydroxy-4-(4-phenyl-butyrylamino)-benzamide

Drug Info

[53]

187

N-Hydroxy-4-(5-phenyl-pentanoylamino)-benzamide

Drug Info

[53]

188

N-Hydroxy-4-(phenylacetylamino-methyl)-benzamide

Drug Info

[54]

189

N-Hydroxy-4-phenylacetylamino-benzamide

Drug Info

[53]

190

N-hydroxy-5-(pyridin-2-yl)thiophene-2-carboxamide

Drug Info

[68]

191

N-hydroxy-5-(pyridin-3-yl)thiophene-2-carboxamide

Drug Info

[68]

192

N-hydroxy-5-(pyridin-4-yl)thiophene-2-carboxamide

Drug Info

[68]

193

N-hydroxy-5-phenylthiophene-2-carboxamide

Drug Info

[68]

194

N-hydroxy-6-oxo-6-phenylhexanamide

Drug Info

[67]

195

N-hydroxy-7-(4-methoxyphenyl)-7-oxoheptanamide

Drug Info

[67]

196

N-hydroxy-7-(naphthalen-2-yl)-7-oxoheptanamide

Drug Info

[67]

197

N-hydroxy-7-(naphthalen-2-yloxy)heptanamide

Drug Info

[63]

198

N-hydroxy-7-oxo-7-phenylheptanamide

Drug Info

[67]

199

N-hydroxy-8-(2-methoxyphenyl)-8-oxooctanamide

Drug Info

[67]

200

N-hydroxy-8-(4-methoxyphenyl)-8-oxooctanamide

Drug Info

[67]

201

N-hydroxy-8-(naphthalen-2-yl)non-8-enamide

Drug Info

[67]

202

N-hydroxy-8-(naphthalen-2-yl)oct-7-enamide

Drug Info

[67]

203

N-hydroxy-8-(naphthalen-2-yl)octanamide

Drug Info

[67]

204

N-hydroxy-8-oxo-8-(pyridin-3-yl)octanamide

Drug Info

[67]

205

N-Hydroxy-N'-(2-methylphenyl)octanediamide

Drug Info

[74]

206

N-Hydroxy-N'-(3-methylphenyl)octanediamide

Drug Info

[74]

207

N-Hydroxy-N'-(4-methoxyphenyl)octanediamide

Drug Info

[74]

208

N-Hydroxy-N'-(4-methylphenyl)octanediamide

Drug Info

[74]

209

N-hydroxybenzo[b]thiophene-2-carboxamide

Drug Info

[80]

210

N1-(biphenyl-3-yl)-N8-hydroxyoctanediamide

Drug Info

[81]

211

N1-(biphenyl-4-yl)-N8-hydroxyoctanediamide

Drug Info

[82]

212

nexturastat A

Drug Info

[83]

213

NSC-746457

Drug Info

[84]

214

Octanedioic acid bis-hydroxyamide

Drug Info

[85]

215

Octanedioic acid hydroxyamide pyridin-2-ylamide

Drug Info

[57]

216

Octanedioic acid hydroxyamide pyridin-4-ylamide

Drug Info

[57]

217

PSAMMAPLIN A

Drug Info

[55]

218

ST-2986

Drug Info

[86]

219

ST-2987

Drug Info

[86]

220

ST-3050

Drug Info

[86]

221

Thioacetic acid S-(6-phenylcarbamoyl-hexyl) ester

Drug Info

[56]

Modulator

[+] 2 Modulator drugs

HBI-8000

Drug Info

[40]

RG-2833

Drug Info

[40]

Cell-based Target Expression Variations

Top

Cell-based Target Expression Variations

Cell-based Target Expression Variations Info

Drug Binding Sites of Target

Top

Ligand Name: Myo-inositol hexaphosphate

Ligand Info

Structure Description

HDAC1:MTA1 in complex with inositol-6-phosphate and a novel peptide inhibitor based on histone H4

PDB:5ICN

Method

X-ray diffraction

Resolution

3.30 Å

Mutation

[87]

PDB Sequence

RRKVCYYYDG

¹⁷

DVGNYYYGQG

²⁷

HPMKPHRIRM

³⁷

THNLLLNYGL

⁴⁷

YRKMEIYRPH

⁵⁷

KANAEEMTKY

⁶⁷

HSDDYIKFLR

⁷⁷

SIRPDNMSEY

⁸⁷

SKQMQRFNVG

⁹⁷

EDCPVFDGLF

¹⁰⁷

EFCQLSTGGS

¹¹⁷

VASAVKLNKQ

¹²⁷

QTDIAVNWAG

¹³⁷

GLHHAKKSEA

¹⁴⁷

SGFCYVNDIV

¹⁵⁷

LAILELLKYH

¹⁶⁷

QRVLYIDIDI

¹⁷⁷

HHGDGVEEAF

¹⁸⁷

YTTDRVMTVS

¹⁹⁷

FHKYGEYFPG

²⁰⁷

TGDLRDIGAG

²¹⁷

KGKYYAVNYP

²²⁷

LRDGIDDESY

²³⁷

EAIFKPVMSK

²⁴⁷

VMEMFQPSAV

²⁵⁷

VLQCGSDSLS

²⁶⁷

GDRLGCFNLT

²⁷⁷

IKGHAKCVEF

²⁸⁷

VKSFNLPMLM

²⁹⁷

LGGGGYTIRN

³⁰⁷

VARCWTYETA

³¹⁷

VALDTEIPNE

³²⁷

LPYNDYFEYF

³³⁷

GPDFKLHISP

³⁴⁷

SNMTNQNTNE

³⁵⁷

YLEKIKQRLF

³⁶⁷

ENLRMLPHA

Residue

Distance (Å)

TYR23

4.356

GLN26

4.874

GLY27

3.382

HIS28

4.240

Residue

Distance (Å)

LYS31

3.097

ARG270

3.355

ILE305

3.513

ARG306

4.291

Click to View More Binding Site Information of This Target and Ligand Pair

Ligand Name: (2S)-2-amino-8-(hydroxyamino)-8-oxooctanoic acid

Ligand Info

Structure Description

HDAC1:MTA1 in complex with inositol-6-phosphate and a novel peptide inhibitor based on histone H4

PDB:5ICN

Method

X-ray diffraction

Resolution

3.30 Å

Mutation

[87]

PDB Sequence

RRKVCYYYDG

¹⁷

DVGNYYYGQG

²⁷

HPMKPHRIRM

³⁷

THNLLLNYGL

⁴⁷

YRKMEIYRPH

⁵⁷

KANAEEMTKY

⁶⁷

HSDDYIKFLR

⁷⁷

SIRPDNMSEY

⁸⁷

SKQMQRFNVG

⁹⁷

EDCPVFDGLF

¹⁰⁷

EFCQLSTGGS

¹¹⁷

VASAVKLNKQ

¹²⁷

QTDIAVNWAG

¹³⁷

GLHHAKKSEA

¹⁴⁷

SGFCYVNDIV

¹⁵⁷

LAILELLKYH

¹⁶⁷

QRVLYIDIDI

¹⁷⁷

HHGDGVEEAF

¹⁸⁷

YTTDRVMTVS

¹⁹⁷

FHKYGEYFPG

²⁰⁷

TGDLRDIGAG

²¹⁷

KGKYYAVNYP

²²⁷

LRDGIDDESY

²³⁷

EAIFKPVMSK

²⁴⁷

VMEMFQPSAV

²⁵⁷

VLQCGSDSLS

²⁶⁷

GDRLGCFNLT

²⁷⁷

IKGHAKCVEF

²⁸⁷

VKSFNLPMLM

²⁹⁷

LGGGGYTIRN

³⁰⁷

VARCWTYETA

³¹⁷

VALDTEIPNE

³²⁷

LPYNDYFEYF

³³⁷

GPDFKLHISP

³⁴⁷

SNMTNQNTNE

³⁵⁷

YLEKIKQRLF

³⁶⁷

ENLRMLPHA

Residue

Distance (Å)

ASP99

2.886

HIS140

3.062

HIS141

3.055

GLY149

3.686

PHE150

3.435

CYS151

4.972

ASP176

2.979

HIS178

3.181

Residue

Distance (Å)

PHE205

3.729

GLN260

4.566

ASP264

2.755

LEU271

4.141

GLY300

4.138

GLY301

3.093

GLY302

4.623

TYR303

2.660

Click to View More Binding Site Information of This Target with Different Ligands

Different Human System Profiles of Target	Top
Human Similarity Proteins of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target. A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs (Brief Bioinform, 21: 649-662, 2020). Human Tissue Distribution of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues. The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects (Nat Rev Drug Discov, 20: 64-81, 2021). Human Pathway Affiliation of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function. Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes (Pharmacol Rev, 58: 259-279, 2006). Biological Network Descriptors of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database. The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information (Front Pharmacol, 9, 1245, 2018; Curr Opin Struct Biol. 44:134-142, 2017). Human Similarity Proteins Human Tissue Distribution Human Pathway Affiliation Biological Network Descriptors

Different Human System Profiles of Target

Top

Human Similarity Proteins of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.

A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs (Brief Bioinform, 21: 649-662, 2020).

Human Tissue Distribution of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues.

The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects (Nat Rev Drug Discov, 20: 64-81, 2021).

Human Pathway Affiliation of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.

Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes (Pharmacol Rev, 58: 259-279, 2006).

Biological Network Descriptors of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.

The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information (Front Pharmacol, 9, 1245, 2018; Curr Opin Struct Biol. 44:134-142, 2017).

Human Similarity Proteins

Human Tissue Distribution

Human Pathway Affiliation

Biological Network Descriptors

There is no similarity protein (E value < 0.005) for this target


Note: If a protein has TS (tissue specficity) scores at least in one tissue >= 2.5, this protein is called tissue-enriched (including tissue-enriched-but-not-specific and tissue-specific). In the plots, the vertical lines are at thresholds 2.5 and 4.

KEGG Pathway	Pathway ID	Affiliated Target
Cell cycle	hsa04110	Affiliated Target
Class: Cellular Processes => Cell growth and death	Pathway Hierarchy
Longevity regulating pathway - multiple species	hsa04213	Affiliated Target
Class: Organismal Systems => Aging	Pathway Hierarchy
Notch signaling pathway	hsa04330	Affiliated Target
Class: Environmental Information Processing => Signal transduction	Pathway Hierarchy
Neutrophil extracellular trap formation	hsa04613	Affiliated Target
Class: Organismal Systems => Immune system	Pathway Hierarchy
Thyroid hormone signaling pathway	hsa04919	Affiliated Target
Class: Organismal Systems => Endocrine system	Pathway Hierarchy

Degree	166	Degree centrality	1.78E-02	Betweenness centrality	2.19E-02
Closeness centrality	2.78E-01	Radiality	1.47E+01	Clustering coefficient	6.11E-02
Neighborhood connectivity	3.19E+01	Topological coefficient	1.82E-02	Eccentricity	11
Download	Click to Download the Full PPI Network of This Target

Chemical Structure based Activity Landscape of Target

Top

Drug Property Profile of Target

Top

(1) Molecular Weight (mw) based Drug Clustering

(2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering

(3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering

(4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering

(5) Rotatable Bond Count (rotbonds) based Drug Clustering

(6) Topological Polar Surface Area (polararea) based Drug Clustering

"RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five

Co-Targets

Top

Co-Targets

Co-Targets Info

Target Poor or Non Binders

Top

Target Poor or Non Binders

Target Poor or Non Binders Info

Target Regulators

Top

Target-regulating microRNAs

Target-regulating microRNAs Info

Target-interacting Proteins

Target-interacting Proteins Info

Target Profiles in Patients

Top

Target Expression
Profile (TEP)

Target Expression Profile Info

Target Affiliated Biological Pathways		Top
KEGG Pathway	[+] 12 KEGG Pathways	+
1	Cell cycle
2	Notch signaling pathway
3	Thyroid hormone signaling pathway
4	Huntington's disease
5	Amphetamine addiction
6	Alcoholism
7	Epstein-Barr virus infection
8	Pathways in cancer
9	Transcriptional misregulation in cancer
10	Viral carcinogenesis
11	MicroRNAs in cancer
12	Chronic myeloid leukemia
NetPath Pathway	[+] 1 NetPath Pathways	+
1	TCR Signaling Pathway
Panther Pathway	[+] 2 Panther Pathways	+
1	Wnt signaling pathway
2	p53 pathway
PID Pathway	[+] 17 PID Pathways	+
1	Regulation of nuclear SMAD2/3 signaling
2	Notch signaling pathway
3	E2F transcription factor network
4	Presenilin action in Notch and Wnt signaling
5	Signaling events mediated by HDAC Class I
6	Regulation of Telomerase
7	Glucocorticoid receptor regulatory network
8	Sumoylation by RanBP2 regulates transcriptional repression
9	Regulation of Androgen receptor activity
10	IL3-mediated signaling events
11	Validated nuclear estrogen receptor alpha network
12	Retinoic acid receptors-mediated signaling
13	Hedgehog signaling events mediated by Gli proteins
14	Regulation of nuclear beta catenin signaling and target gene transcription
15	Validated targets of C-MYC transcriptional repression
16	Regulation of retinoblastoma protein
17	Notch-mediated HES/HEY network
Reactome	[+] 12 Reactome Pathways	+
1	G0 and Early G1
2	p75NTR negatively regulates cell cycle via SC1
3	Formation of the beta-catenin:TCF transactivating complex
4	NOTCH1 Intracellular Domain Regulates Transcription
5	SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription
6	Constitutive Signaling by NOTCH1 PEST Domain Mutants
7	Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants
8	HDACs deacetylate histones
9	Deactivation of the beta-catenin transactivating complex
10	NoRC negatively regulates rRNA expression
11	RNA Polymerase I Transcription Initiation
12	Factors involved in megakaryocyte development and platelet production
WikiPathways	[+] 17 WikiPathways	+
1	SIDS Susceptibility Pathways
2	Notch Signaling Pathway
3	TGF beta Signaling Pathway
4	IL-6 signaling pathway
5	Apoptosis-related network due to altered Notch3 in ovarian cancer
6	Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer
7	Notch Signaling Pathway
8	Retinoblastoma (RB) in Cancer
9	Neural Crest Differentiation
10	TWEAK Signaling Pathway
11	Integrated Breast Cancer Pathway
12	Signalling by NGF
13	RNA Polymerase I, RNA Polymerase III, and Mitochondrial Transcription
14	Mitotic G1-G1/S phases
15	Factors involved in megakaryocyte development and platelet production
16	Cell Cycle
17	Androgen receptor signaling pathway

Target-Related Models and Studies

Top

Target Validation

Target Validation Info

Target QSAR Model

References

Top

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