Target Information

Target General Infomation
Target ID
T68536
Former ID
TTDS00308
Target Name
Tubulin beta
Synonyms
Beta-tubulin; Congopain; Cruzaine; Cysteine proteinase cruzipain; Major cysteine proteinase; Tubulin beta-1 chain
Target Type
Successful
Disease Acute lymphoblastic leukemia [ICD9: 204.0, 556; ICD10: C91.0]
Breast cancer [ICD9: 174, 175; ICD10: C50]
Cancer [ICD9: 140-229; ICD10: C00-C96]
Glioblastoma multiforme [ICD9: 191; ICD10: C71]
Mesothelioma [ICD9: 163; ICD10: C45]
Non-small cell lung cancer [ICD10: C33-C34]
Solid tumours [ICD9: 140-199, 210-229; ICD10: C00-D48]
Worm infections [ICD9: 120-129; ICD10: B65-B83]
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.
BioChemical Class
Tubulin family
Target Validation
T68536
EC Number
EC 3.4.22.51
Drugs and Mode of Action
Drug(s) Albendazole Drug Info Approved Worm infections [536135]
Mebendazole Drug Info Approved Worm infections [536224]
Oral paclitaxel Drug Info Approved Cancer [551871]
Taxol Drug Info Approved Breast carcinoma [530307]
Vincristine Drug Info Approved Acute lymphoblastic leukemia [536556], [541865]
Vindesine Drug Info Approved Acute lymphoblastic leukemia [536361], [551871]
Liposomal encapsulated paclitaxel (LEP) Drug Info Phase 3 Cancer [551035]
Sphingosome Encapsulated Vinorelbine Drug Info Phase 3 Solid tumours [522410]
Batabulin Drug Info Phase 2/3 Cancer [521550]
ABT-751 Drug Info Phase 2 Solid tumours [521967]
BNC-105 Drug Info Phase 2 Mesothelioma [547995]
DOLASTATIN-10 Drug Info Phase 2 Cancer [521453]
Lexibulin iv infusion Drug Info Phase 2 Glioblastoma multiforme [522301]
Plinabulin Drug Info Phase 2 Non-small cell lung cancer [549687]
T-607 Drug Info Phase 2 Cancer [521548]
Verubulin Drug Info Phase 2 Solid tumours [523339]
ZD-6126 Drug Info Phase 2 Cancer [521567]
BAL-101553 Drug Info Phase 1/2 Cancer [525257]
1069C Drug Info Phase 1 Cancer [534331]
ABI-011 Drug Info Phase 1 Solid tumours [523113]
ALB-109564(a) Drug Info Phase 1 Solid tumours [522388]
CKD-516 Drug Info Phase 1 Solid tumours [523842]
DAVLB-HYDRAZIDE Drug Info Phase 1 Cancer [530726]
NSC-639829 Drug Info Phase 1 Cancer [544019]
Simotaxel Drug Info Phase 1 Cancer [521789]
STA-5312 Drug Info Phase 1 Cancer [521784]
Tasidotin hydrochloride Drug Info Phase 1 Cancer [528421]
KOS-1803 Drug Info Preclinical Cancer [548297]
CEMADOTIN HYDROCHLORIDE Drug Info Discontinued in Phase 2 Cancer [546200]
Epothilone D Drug Info Discontinued in Phase 2 Breast cancer [547385]
RHIZOXIN Drug Info Discontinued in Phase 2 Breast cancer [544988]
S-12363 Drug Info Discontinued in Phase 2 Cancer [544756]
Denibulin Drug Info Discontinued in Phase 1 Cancer [548126]
Modulator 1069C Drug Info [550941], [551871]
ABI-011 Drug Info
ABT-751 Drug Info [1572591]
ALB-109564(a) Drug Info
APH-0911 Drug Info [543674]
ARC-200 Drug Info [543674]
BNC-105 Drug Info
CEMADOTIN HYDROCHLORIDE Drug Info [534776], [551871]
DAVLB-HYDRAZIDE Drug Info [544311], [551871]
IDN-5390 Drug Info [543674]
Isoquinoline alkaloids Drug Info [543674]
Liposomal encapsulated paclitaxel (LEP) Drug Info [526031], [530307]
NSC-639829 Drug Info [526117], [551871]
Oral paclitaxel Drug Info [526031], [530307]
Plinabulin Drug Info
S-12363 Drug Info [550022]
Sphingosome Encapsulated Vinorelbine Drug Info [529890]
Taxol Drug Info [530307]
Verubulin Drug Info
Vincristine Drug Info [556264]
XN-0502 Drug Info [543674]
Inhibitor 2'-amino-3,4,4',5-tetramethoxy-(Z)-stillbene Drug Info [528474]
2,3'-diamino-3,4,4',5-tetramethoxy-(Z)-stillbene Drug Info [528474]
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-amino-3,4',5-trimethoxy-(Z)-stillbene Drug Info [528474]
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]
3,4',5-trimethoxy-(Z)-stilbene Drug Info [528474]
3,4,4',5-tetramethoxy-(Z)-stilbene Drug Info [528474]
3-bromo-4,4',5-trimethoxy-(Z)-stilbene Drug Info [528474]
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-ile-ustiloxin Drug Info [528306]
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]
BAL-101553 Drug Info [533035]
Batabulin Drug Info [526170]
CENTAUREIDIN Drug Info [534652]
CKD-516 Drug Info [532537]
COLCHINOL Drug Info [527777]
COMBETASTATIN Drug Info [534795]
Denibulin Drug Info [544311]
DOLASTATIN-10 Drug Info [528306]
Epothilone D Drug Info [551393]
GNF-PF-117 Drug Info [534009]
Isopropyl 3-(phenylthio)-1H-indole-2-carboxylate Drug Info [527999]
KOS-1803 Drug Info [543674]
Lexibulin iv infusion Drug Info [550425]
MR-22388 Drug Info [526982]
MYOSEVERIN Drug Info [526222]
N-(4-(3-(pyridin-2-yl)acryloyl)phenyl)acetamide Drug Info [528428]
NSC-106970 Drug Info [534652]
NSC-664171 Drug Info [534600]
NSC-679036 Drug Info [534469]
ON-24160 Drug Info [543674]
PHENSTATIN Drug Info [526346]
RHIZOXIN Drug Info [528337]
RTA-301 Drug Info [543674]
Simotaxel Drug Info [543674]
STA-5312 Drug Info [550066], [551871]
T-607 Drug Info [551628]
THIOCOLCHICINE Drug Info [534060]
TL-1892 Drug Info [543674]
USTILOXIN A Drug Info [528306]
Ustiloxin D Drug Info [528306]
Ustiloxin F Drug Info [528306]
ZD-6126 Drug Info [529270]
Binder Albendazole Drug Info [537193]
Mebendazole Drug Info [537193]
Tasidotin hydrochloride Drug Info [536891]
Vindesine Drug Info [536411], [536504]
Pathways
KEGG Pathway Phagosome
Gap junction
Pathogenic Escherichia coli infection
NetPath Pathway FSH Signaling Pathway
TCR Signaling Pathway
EGFR1 Signaling Pathway
PANTHER Pathway Cytoskeletal regulation by Rho GTPase
Huntington disease
Reactome Regulation of PLK1 Activity at G2/M Transition
Loss of Nlp from mitotic centrosomes
Recruitment of mitotic centrosome proteins and complexes
Loss of proteins required for interphase microtubule organization?from the centrosome
Anchoring of the basal body to the plasma membrane
WikiPathways Parkin-Ubiquitin Proteasomal System pathway
Pathogenic Escherichia coli infection
Mitotic G2-G2/M phases
References
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Ref 521550ClinicalTrials.gov (NCT00057382) T138067 Versus Doxorubicin in Chemotherapy-Naive, Unresectable, Hepatocellular Carcinoma Patients. U.S. National Institutes of Health.
Ref 521567ClinicalTrials.gov (NCT00065572) Exploratory Study to Assess the Biological Activity of ZD6126 in Subjects With Newly Diagnosed Metastatic Renal Cell Carcinoma (Stage IV). U.S. National Institutes ofHealth.
Ref 521784ClinicalTrials.gov (NCT00276913) A Phase I Study of STA-5312 in Subjects With Advanced or Metastatic Solid Tumors. U.S. National Institutes of Health.
Ref 521789ClinicalTrials.gov (NCT00277836) Study Evaluating MST-997 in Advanced Malignant Solid Tumors. U.S. National Institutes of Health.
Ref 521967ClinicalTrials.gov (NCT00436852) ABT-751 in Treating Children With Neuroblastoma That Has Relapsed or Not Responded to Previous Treatment. U.S. National Institutes of Health.
Ref 522301ClinicalTrials.gov (NCT00664378) Efficacy Study of CYT997 in Multiple Myeloma. U.S. National Institutes of Health.
Ref 522388ClinicalTrials.gov (NCT00724100) A Trial of ALB 109564(a) in Subjects With Advanced Solid Tumors. U.S. National Institutes of Health.
Ref 522410ClinicalTrials.gov (NCT00737867) Vinorelbine/Gemcitabine Versus Vinorelbine/Carboplatin in Advanced Non-small Cell Lung Cancer. U.S. National Institutes of Health.
Ref 523113ClinicalTrials.gov (NCT01163071) A Phase 1 Trial of ABI-011 in Patients With Advanced Solid Tumors or Lymphomas. U.S. National Institutes of Health.
Ref 523339ClinicalTrials.gov (NCT01285414) Verubulin, Radiation Therapy, and Temozolomide to Treat Patients With Newly Diagnosed Glioblastoma Multiforme. U.S. National Institutes of Health.
Ref 523842ClinicalTrials.gov (NCT01560325) Safety Study of Increasing Doses of CKD-516 in Patients With Advanced Solid Cancers. U.S. National Institutes of Health.
Ref 525257ClinicalTrials.gov (NCT02490800) Phase 1/2a Study of Oral BAL101553 in Adult Patients With Solid Tumors.
Ref 528421Phase I and pharmacokinetic study of tasidotin hydrochloride (ILX651), a third-generation dolastatin-15 analogue, administered weekly for 3 weeks every 28 days in patients with advanced solid tumors.Clin Cancer Res. 2006 Sep 1;12(17):5207-15.
Ref 530307Paclitaxel directly binds to Bcl-2 and functionally mimics activity of Nur77. Cancer Res. 2009 Sep 1;69(17):6906-14.
Ref 530726The human immune response to KS1/4-desacetylvinblastine (LY256787) and KS1/4-desacetylvinblastine hydrazide (LY203728) in single and multiple dose clinical studies. Cancer Res. 1991 May 1;51(9):2286-90.
Ref 534331Phase I trial and pharmacokinetics of the tubulin inhibitor 1069C85--a synthetic agent binding at the colchicine site designed to overcome multidrug resistance. Br J Cancer. 1997;75(4):608-13.
Ref 536135Opportunities and challenges in antiparasitic drug discovery. Nat Rev Drug Discov. 2005 Sep;4(9):727-40.
Ref 536224Emerging drugs for irritable bowel syndrome. Expert Opin Emerg Drugs. 2006 May;11(2):293-313.
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 536556Vinflunine, a novel microtubule inhibitor, suppresses calmodulin interaction with the microtubule-associated protein STOP. Biochemistry. 2007 Dec 25;46(51):14899-906. Epub 2007 Dec 4.
Ref 541865(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: 6785).
Ref 544019Phase I Study of Continuous Weekly Dosing of Dimethylamino Benzoylphenylurea (BPU) in Patients with Solid Tumours. Eur J Cancer. 2007 January; 43(1): 78-86.
Ref 544756Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000879)
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)
Ref 546200Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800006853)
Ref 547385Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800015773)
Ref 547995Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800021025)
Ref 548126Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800022182)
Ref 548297Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800024256)
Ref 549687J Clin Oncol 32:5s, 2014 (suppl, abstr 8054).
Ref 551035Clinical pipeline report, company report or official report of Insys Therapeutics.
Ref 551871Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
Ref
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Ref 525946Bioorg Med Chem Lett. 2001 Jan 8;11(1):51-4.Antimitotic and cell growth inhibitory properties of combretastatin A-4-like ethers.
Ref 526031The binding conformation of Taxol in beta-tubulin: a model based on electron crystallographic density. Proc Natl Acad Sci U S A. 2001 Apr 24;98(9):5312-6. Epub 2001 Apr 17.
Ref 526117Solubilization of NSC-639829. Int J Pharm. 2001 Aug 28;225(1-2):41-7.
Ref 526170Hydrophilic, pro-drug analogues of T138067 are efficacious in controlling tumor growth in vivo and show a decreased ability to cross the blood brain barrier. J Med Chem. 2001 Oct 25;44(22):3599-605.
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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 528306Bioorg Med Chem Lett. 2006 Sep 15;16(18):4804-7. Epub 2006 Jul 11.Total synthesis and biological evaluation of ustiloxin natural products and two analogs.
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Ref 529270Phase I clinical evaluation of ZD6126, a novel vascular-targeting agent, in patients with solid tumors. Invest New Drugs. 2008 Apr;26(2):159-67.
Ref 529890Liposomal-encapsulated doxorubicin (Myocet; D-99) and vinorelbine in previously treated metastatic breast cancer patients: a feasibility study. Tumori. 2008 Sep-Oct;94(5):686-90.
Ref 530307Paclitaxel directly binds to Bcl-2 and functionally mimics activity of Nur77. Cancer Res. 2009 Sep 1;69(17):6906-14.
Ref 532537CKD-516 displays vascular disrupting properties and enhances anti-tumor activity in combination with chemotherapy in a murine tumor model. Invest New Drugs. 2014 Jun;32(3):400-11.
Ref 533035Initial testing (stage 1) of BAL101553, a novel tubulin binding agent, by the pediatric preclinical testing program. Pediatr Blood Cancer. 2015 Jun;62(6):1106-9.
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 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.
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 534776Suppression of microtubule dynamics by binding of cemadotin to tubulin: possible mechanism for its antitumor action. Biochemistry. 1998 Dec 15;37(50):17571-8.
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Ref 536411Antiproliferating activity of the mitotic inhibitor pironetin against vindesine- and paclitaxel-resistant human small cell lung cancer H69 cells. Anticancer Res. 2007 Mar-Apr;27(2):729-36.
Ref 536504Gene signatures developed from patient tumor explants grown in nude mice to predict tumor response to 11 cytotoxic drugs. Cancer Genomics Proteomics. 2007 May-Jun;4(3):197-209.
Ref 536891Intracellular activation and deactivation of tasidotin, an analog of dolastatin 15: correlation with cytotoxicity. Mol Pharmacol. 2009 Jan;75(1):218-26. Epub 2008 Oct 16.
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Ref 544311An Overview of Tubulin Inhibitors That Interact with the Colchicine Binding Site. Pharm Res. 2012 November; 29(11): 2943-2971.
Ref 550022Microtubule assembly protects the region 28-38 of the beta- tubulin subunit. Article first published online: 4 FEB 2005.
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