Target General Infomation
Target ID
T43189
Former ID
TTDS00271
Target Name
Tubulin
Gene Name
TUBB3
Synonyms
Tubulin beta-4 chain; Tubulin beta-III; TUBB3
Target Type
Successful
Disease Acute gouty arthritis [ICD9: 274; ICD10: M10]
Actinic keratosis [ICD9: 702; ICD10: L57.0]
Advanced sarcomar [ICD10: C96.4]
Advanced breast cancer [ICD9: 174, 175; ICD10: C50]
Breast cancer; Prostate cancer [ICD9:174, 175, 185; ICD10: C50, C61]
Breast cancer; Ovarian cancer [ICD9: 174, 175, 183; ICD10: C50, C56]
Breast cancer [ICD9: 174, 175; ICD10: C50]
Central nervous system disease [ICD10: G00-G99]
Cancer [ICD9: 140-229; ICD10: C00-C96]
Immuno-suppressant [ICD10: T86.0]
Ovarian cancer [ICD9: 183; ICD10: C56]
Pancreatic cancer; Bladder cancer [ICD9: 188; ICD10: C25, C67]
Solid tumours [ICD9: 140-199, 210-229; ICD10: C00-D48]
Function
Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain. TUBB3 plays a critical role in proper axon guidance and mantainance.
BioChemical Class
Tubulin family
Target Validation
T43189
UniProt ID
Sequence
MREIVHIQAGQCGNQIGAKFWEVISDEHGIDPSGNYVGDSDLQLERISVYYNEASSHKYV
PRAILVDLEPGTMDSVRSGAFGHLFRPDNFIFGQSGAGNNWAKGHYTEGAELVDSVLDVV
RKECENCDCLQGFQLTHSLGGGTGSGMGTLLISKVREEYPDRIMNTFSVVPSPKVSDTVV
EPYNATLSIHQLVENTDETYCIDNEALYDICFRTLKLATPTYGDLNHLVSATMSGVTTSL
RFPGQLNADLRKLAVNMVPFPRLHFFMPGFAPLTARGSQQYRALTVPELTQQMFDAKNMM
AACDPRHGRYLTVATVFRGRMSMKEVDEQMLAIQSKNSSYFVEWIPNNVKVAVCDIPPRG
LKMSSTFIGNSTAIQELFKRISEQFTAMFRRKAFLHWYTGEGMDEMEFTEAESNMNDLVS
EYQQYQDATAEEEGEMYEDDEEESEAQGPK
Drugs and Mode of Action
Drug(s) Cabazitaxel Drug Info Approved Breast cancer; Prostate cancer [531351], [541879]
Colchicine Drug Info Approved Acute gouty arthritis [538354], [542532], [551871]
Docetaxel Drug Info Approved Cancer [536361], [541891]
Eribulin Drug Info Approved Breast cancer [531351], [541895]
Ixabepilone Drug Info Approved Advanced breast cancer [529282], [531351], [541906]
Vinorelbine Drug Info Approved Cancer [536361], [542112]
Epothilon Drug Info Phase 3 Breast cancer; Ovarian cancer [536839]
BMS-184476 Drug Info Phase 2 Cancer [527405]
BMS-188797 Drug Info Phase 2 Cancer [521476], [527913]
BMS-275183 Drug Info Phase 2 Cancer [521864]
Cabazitaxel Drug Info Phase 2 Solid tumours [531351], [541879]
CRYPTOPHYCIN 52 Drug Info Phase 2 Cancer [526539]
DOLASTATIN-10 Drug Info Phase 2 Cancer [521453]
Indibulin Drug Info Phase 2 Advanced sarcomar [551789]
Milataxel Drug Info Phase 2 Cancer [522328]
Soblidotin Drug Info Phase 2 Cancer [521565]
E 7974 Drug Info Phase 1 Ovarian cancer [536839]
SDZ-LAV-694 Drug Info Phase 1 Actinic keratosis [530311]
ABI-013 Drug Info Preclinical Cancer [549895]
Epothilone B Drug Info Discontinued in Phase 3 Cancer [546007]
Larotaxel Drug Info Discontinued in Phase 3 Pancreatic cancer; Bladder cancer [546774]
ATX-201 Drug Info Discontinued in Phase 2 Actinic keratosis [548552]
Cryptophycin Drug Info Discontinued in Phase 2 Discovery agent [545698]
ERBULOZOLE Drug Info Discontinued in Phase 2 Cancer [545429]
RHIZOXIN Drug Info Discontinued in Phase 2 Breast cancer [544988]
ABJ-879 Drug Info Discontinued in Phase 1 Cancer [547922]
Discodermolide Drug Info Discontinued in Phase 1 Immuno-suppressant [546438]
FCE-28161 Drug Info Discontinued in Phase 1 Cancer [546352]
TALTOBULIN Drug Info Discontinued in Phase 1 Cancer [547769]
21-AMINOEPOTHILONE B Drug Info Terminated Cancer [547539]
Docetaxel Drug Info Investigative Cancer [536155]
Inhibitor 2-(3-Chloro-phenyl)-1H-[1,8]naphthyridin-4-one Drug Info [534469]
2-(4-Methoxy-phenyl)-1H-indole-3-carbaldehyde Drug Info [534765]
2-Furan-2-yl-7-methyl-1H-[1,8]naphthyridin-4-one Drug Info [525604]
2-m-Tolyl-1H-[1,8]naphthyridin-4-one Drug Info [534469]
2-Methoxy-5-(3,4,5-trimethoxy-benzyl)-phenol Drug Info [527276]
2-Methoxy-5-(3,4,5-trimethoxy-phenoxy)-phenol Drug Info [525946]
2-Methoxy-5-(5,6,7-trimethoxy-indan-1-yl)-phenol Drug Info [525450]
2-Naphthalen-1-yl-1H-[1,8]naphthyridin-4-one Drug Info [534469]
2-Naphthalen-2-yl-1H-[1,8]naphthyridin-4-one Drug Info [534469]
21-AMINOEPOTHILONE B Drug Info [544107], [551871]
5,7-Dimethyl-2-m-tolyl-1H-[1,8]naphthyridin-4-one Drug Info [534469]
5-Methyl-2-m-tolyl-1H-[1,8]naphthyridin-4-one Drug Info [534469]
6-Methyl-2-m-tolyl-1H-[1,8]naphthyridin-4-one Drug Info [534469]
7-Methyl-2-m-tolyl-1H-[1,8]naphthyridin-4-one Drug Info [534469]
ATX-201 Drug Info [551080]
BMS-184476 Drug Info [544055], [551871]
BMS-188797 Drug Info [526881], [551871]
BMS-275183 Drug Info [531077]
Cabazitaxel Drug Info [531351]
CENTAUREIDIN Drug Info [534652]
COLCHINOL Drug Info [527777]
COMBETASTATIN Drug Info [534795]
CRYPTOPHYCIN 52 Drug Info [526539], [551871]
Docetaxel Drug Info [536155]
DOLASTATIN-10 Drug Info [534612]
E 7974 Drug Info [536839]
Epothilone B Drug Info [537114]
Eribulin Drug Info [531351]
GNF-PF-117 Drug Info [534009]
Isopropyl 3-(phenylthio)-1H-indole-2-carboxylate Drug Info [527999]
Larotaxel Drug Info [549823]
Milataxel Drug Info [549708]
MR-22388 Drug Info [526982]
MYOSEVERIN Drug Info [526222]
NSC-106970 Drug Info [534652]
NSC-664171 Drug Info [534600]
NSC-679036 Drug Info [534469]
PHENSTATIN Drug Info [526346]
RHIZOXIN Drug Info [528337]
SDZ-LAV-694 Drug Info [551570], [551871]
TALTOBULIN Drug Info [530691], [551871]
THIOCOLCHICINE Drug Info [534060]
Vinorelbine Drug Info [536782]
WR85915 Drug Info [535074]
Modulator ABJ-879 Drug Info [528961]
AL-209 Drug Info [531541]
AL-309 Drug Info [531541]
Discodermolide Drug Info [534515]
ERBULOZOLE Drug Info [533220], [551871]
FCE-28161 Drug Info [550854], [551871]
Soblidotin Drug Info [528298]
Binder Colchicine Drug Info [537471]
Inducer Cryptophycin Drug Info [536415]
Eleutherobin Drug Info [538088]
Sarcodictyin A Drug Info [534859]
Stablizer Epothilon Drug Info [536839]
Indibulin Drug Info [551789]
Ixabepilone Drug Info [531351]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
References
Ref 521453ClinicalTrials.gov (NCT00003677) Dolastatin 10 in Treating Patients With Metastatic Pancreatic Cancer. U.S. National Institutes of Health.
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Ref 521864ClinicalTrials.gov (NCT00359450) Study of BMS-275183 in Patients With Pretreated Locally Advanced or Metastatic NSCLC (Non Small Cell Lung Cancer). U.S. National Institutes of Health.
Ref 522328ClinicalTrials.gov (NCT00685204) An Efficacy Study of Milataxel (TL139) Administered Orally for Malignant Mesothelioma. U.S. National Institutes of Health.
Ref 526539Phase 2 study of cryptophycin 52 (LY355703) in patients previously treated with platinum based chemotherapy for advanced non-small cell lung cancer. Lung Cancer. 2003 Feb;39(2):197-9.
Ref 527405Phase II trial of the novel taxane BMS-184476 as second-line in non-small-cell lung cancer. Ann Oncol. 2005 Apr;16(4):597-601. Epub 2005 Jan 31.
Ref 527913A phase I and pharmacokinetic study of novel taxane BMS-188797 and cisplatin in patients with advanced solid tumours. Br J Cancer. 2006 Jan 16;94(1):79-84.
Ref 5292822007 FDA drug approvals: a year of flux. Nat Rev Drug Discov. 2008 Feb;7(2):107-9.
Ref 530311Recent patents reveal microtubules as persistent promising target for novel drug development for cancers. Recent Pat Antiinfect Drug Discov. 2009 Nov;4(3):164-82.
Ref 531351Mullard A: 2010 FDA drug approvals. Nat Rev Drug Discov. 2011 Feb;10(2):82-5.
Ref 536155Docetaxel: a review of its use in metastatic breast cancer. Drugs. 2005;65(17):2513-31.
Ref 536361Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77. Epub 2007 Feb 20.
Ref 536839Emerging drugs for ovarian cancer. Expert Opin Emerg Drugs. 2008 Sep;13(3):523-36.
Ref 538354FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (ANDA) 084279.
Ref 541879(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6798).
Ref 541891(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6809).
Ref 541895(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6813).
Ref 541906(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6824).
Ref 542112(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7105).
Ref 542532(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7526).
Ref 544988Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800001808)
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Ref 546438Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800008133)
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Ref 547769Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800019128)
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Ref 549895Clinical pipeline report, company report or official report of Celgene Corporation.
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Ref 525450Bioorg Med Chem Lett. 1999 Feb 8;9(3):407-12.The synthesis and evaluation of temperature sensitive tubulin toxins.
Ref 525604J Med Chem. 1999 Oct 7;42(20):4081-7.Antitumor agents. 196. Substituted 2-thienyl-1,8-naphthyridin-4-ones: their synthesis, cytotoxicity, and inhibition of tubulin polymerization.
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Ref 526222J Med Chem. 2001 Dec 20;44(26):4497-500.Synthesis and biological evaluation of myoseverin derivatives: microtubule assembly inhibitors.
Ref 526346J Med Chem. 2002 Jun 6;45(12):2534-42.Antineoplastic agents. 465. Structural modification of resveratrol: sodium resverastatin phosphate.
Ref 526539Phase 2 study of cryptophycin 52 (LY355703) in patients previously treated with platinum based chemotherapy for advanced non-small cell lung cancer. Lung Cancer. 2003 Feb;39(2):197-9.
Ref 526881Phase I and pharmacokinetic study of BMS-188797, a new taxane analog, administered on a weekly schedule in patients with advanced malignancies. Clin Cancer Res. 2003 Nov 1;9(14):5187-94.
Ref 526982J Med Chem. 2004 Mar 11;47(6):1448-64.Design, synthesis, and evaluation of novel thienopyrrolizinones as antitubulin agents.
Ref 527276J Med Chem. 1992 Mar 20;35(6):1058-67.Synthesis of alkoxy-substituted diaryl compounds and correlation of ring separation with inhibition of tubulin polymerization: differential enhancement of inhibitory effects under suboptimal polymerization reaction conditions.
Ref 527777Bioorg Med Chem Lett. 2005 Dec 1;15(23):5154-9. Epub 2005 Sep 28.Synthesis and structure-activity relationships of 1,2,4-triazoles as a novel class of potent tubulin polymerization inhibitors.
Ref 527999J Med Chem. 2006 Feb 9;49(3):947-54.New arylthioindoles: potent inhibitors of tubulin polymerization. 2. Structure-activity relationships and molecular modeling studies.
Ref 528298Antitumor activity of TZT-1027 (Soblidotin). Anticancer Res. 2006 May-Jun;26(3A):1973-81.
Ref 528337Bioorg Med Chem Lett. 2006 Sep 15;16(18):4748-51. Epub 2006 Jul 25.Tubulin polymerization inhibitors with a fluorinated phthalimide skeleton derived from thalidomide.
Ref 528961Novel tubulin-targeting agents: anticancer activity and pharmacologic profile of epothilones and related analogues. Ann Oncol. 2007 Jul;18 Suppl 5:v9-15.
Ref 530691Absolute configurations of tubulin inhibitors taltobulin (HTI-286) and HTI-042 characterized by X-ray diffraction analysis and NMR studies. Bioorg Med Chem Lett. 2010 Mar 1;20(5):1535-8.
Ref 531077A phase 1 study of BMS-275183, a novel oral analogue of paclitaxel given on a daily schedule to patients with advanced malignancies. Invest New Drugs. 2011 Dec;29(6):1426-31.
Ref 531351Mullard A: 2010 FDA drug approvals. Nat Rev Drug Discov. 2011 Feb;10(2):82-5.
Ref 531541Protection against tauopathy by the drug candidates NAP (davunetide) and D-SAL: biochemical, cellular and behavioral aspects. Curr Pharm Des. 2011;17(25):2603-12.
Ref 533220Influence of the synthetic microtubule inhibitor erbulozole (P.I.N.N.) (R 55 104), a new tubulozole congener, and gamma irradiation on murine tumors in vivo. Eur J Cancer Clin Oncol. 1989 Oct;25(10):1499-504.
Ref 534009J Med Chem. 1993 Apr 30;36(9):1146-56.Synthesis and cytotoxicity of 1,6,7,8-substituted 2-(4'-substituted phenyl)-4-quinolones and related compounds: identification as antimitotic agents interacting with tubulin.
Ref 534060J Med Chem. 1993 Mar 5;36(5):544-51.Antitumor agents. 139. Synthesis and biological evaluation of thiocolchicine analogs 5,6-dihydro-6(S)-(acyloxy)- and 5,6-dihydro-6(S)-[(aroyloxy)methyl]-1,2,3-trimethoxy-9-(methylthio)-8H- cyclohepta[a]naphthalen-8-ones as novel cytotoxic and antimitotic agents.
Ref 534469J Med Chem. 1997 Sep 12;40(19):3049-56.Antitumor agents. 178. Synthesis and biological evaluation of substituted 2-aryl-1,8-naphthyridin-4(1H)-ones as antitumor agents that inhibit tubulin polymerization.
Ref 534515The microtubule-stabilizing agent discodermolide competitively inhibits the binding of paclitaxel (Taxol) to tubulin polymers, enhances tubulin nucleation reactions more potently than paclitaxel, andinhibits the growth of paclitaxel-resistant cells. Mol Pharmacol. 1997 Oct;52(4):613-22.
Ref 534600J Med Chem. 1998 Mar 26;41(7):1155-62.Antitumor agents. 181. Synthesis and biological evaluation of 6,7,2',3',4'-substituted-1,2,3,4-tetrahydro-2-phenyl-4-quinolones as a new class of antimitotic antitumor agents.
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Ref 534652J Med Chem. 1998 Jun 18;41(13):2333-8.Structure-activity requirements for flavone cytotoxicity and binding to tubulin.
Ref 534765J Med Chem. 1998 Dec 3;41(25):4965-72.Methoxy-substituted 3-formyl-2-phenylindoles inhibit tubulin polymerization.
Ref 534795Bioorg Med Chem Lett. 1998 Aug 4;8(15):1997-2000.Asymmetric synthesis of antimitotic combretadioxolane with potent antitumor activity against multi-drug resistant cells.
Ref 534859The coral-derived natural products eleutherobin and sarcodictyins A and B: effects on the assembly of purified tubulin with and without microtubule-associated proteins and binding at the polymer taxoid site. Biochemistry. 1999 Apr 27;38(17):5490-8.
Ref 535074Cellular effects of leishmanial tubulin inhibitors on L. donovani. Mol Biochem Parasitol. 2000 Oct;110(2):223-36.
Ref 536155Docetaxel: a review of its use in metastatic breast cancer. Drugs. 2005;65(17):2513-31.
Ref 536415Single-walled tubulin ring polymers. Biopolymers. 2007 Aug 5-15;86(5-6):424-36.
Ref 536782Vinca alkaloid and MDR1. Gan To Kagaku Ryoho. 2008 Jul;35(7):1086-9.
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Ref 537114Emerging therapies for multiple myeloma. Expert Opin Emerg Drugs. 2009 Mar;14(1):99-127.
Ref 537471Vitamin K3 disrupts the microtubule networks by binding to tubulin: a novel mechanism of its antiproliferative activity. Biochemistry. 2009 Jul 28;48(29):6963-74.
Ref 538088Eleutherobin, a novel cytotoxic agent that induces tubulin polymerization, is similar to paclitaxel (Taxol). Cancer Res. 1998 Mar 15;58(6):1111-5.
Ref 544055Phase I trial of the novel taxane BMS-184476 administered in combination with carboplatin every 21 days. Br J Cancer. 2004 July 19; 91(2): 213-218.
Ref 544107Tubulin-Interactive Natural Products as Anticancer Agents. Correction in: J Nat Prod. 2011 May 27; 74(5): 1352.
Ref 549708J Clin Oncol 28, 2010 (suppl; abstr e13075).
Ref 549756Cardiovascular and CNS safety profile of ABI-013, a novel nanoparticle albumin-bound (nab) analog of docetaxel. Cancer Research. 01/2011; 70(8 Supplement):2617-2617.
Ref 549823Pharma & Vaccines. Product Development Pipeline. April 29 2009.
Ref 550854CN patent application no. 101065129, A combination of n-(3-metoxy-5-methylpyrazin-2-yl)-2-(4-[1,3,4-oxadiazol-2-yl]phenyl)pyridine-3-sulphonamide and an anti-mitotic agent for the treatment of cancer.
Ref 551080Clinical pipeline report, company report or official report of Kythera Biopharmaceuticals.
Ref 551570Recent Patents Reveal Microtubules as Persistent Promising Target for Novel Drug Development for Cancers. Recent Patents on Anti-Infective Drug Discovery 12/2009; 4(3):164-82.
Ref 5517892011 Pipeline of ZioPharm.
Ref 551871Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015

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