Target Information

Target General Information

Top

Target ID

T68536 (Former ID: TTDS00308)

Target Name

Tubulin beta (TUBB)

Synonyms

Major cysteine proteinase; Cysteine proteinase cruzipain; Cruzaine; Congopain; Beta-tubulin

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Gene Name

NO-GeName

Target Type

Successful target

[1]

Disease

[+] 4 Target-related Diseases

Breast cancer [ICD-11: 2C60-2C6Y]

Mature B-cell lymphoma [ICD-11: 2A85]

Parasitic worm infestation [ICD-11: 1F90]

Solid tumour/cancer [ICD-11: 2A00-2F9Z]

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.

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BioChemical Class

Tubulin family

UniProt ID

NOUNIPROTAC

Drugs and Modes of Action

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Approved Drug(s)

[+] 5 Approved Drugs

Albendazole

Drug Info

Approved

Worm infection

[2]

Mebendazole

Drug Info

Approved

Worm infection

[3]

Taxol

Drug Info

Approved

Solid tumour/cancer

[4]

Vincristine

Drug Info

Approved

Acute lymphoblastic leukaemia

[5], [6]

Vindesine

Drug Info

Approved

Acute lymphoblastic leukaemia

[4], [7]

Clinical Trial Drug(s)

[+] 19 Clinical Trial Drugs

Plinabulin

Drug Info

Phase 3

Non-small-cell lung cancer

[8]

Batabulin

Drug Info

Phase 2/3

Solid tumour/cancer

[9]

ABT-751

Drug Info

Phase 2

Solid tumour/cancer

[10]

BNC-105

Drug Info

Phase 2

Mesothelioma

[11]

DOLASTATIN-10

Drug Info

Phase 2

Solid tumour/cancer

[12]

Lexibulin

Drug Info

Phase 2

Glioblastoma multiforme

[13]

T-607

Drug Info

Phase 2

Solid tumour/cancer

[14]

Verubulin

Drug Info

Phase 2

Solid tumour/cancer

[15]

ZD-6126

Drug Info

Phase 2

Solid tumour/cancer

[16]

BAL-101553

Drug Info

Phase 1/2

Solid tumour/cancer

[17]

1069C

Drug Info

Phase 1

Solid tumour/cancer

[18]

ABI-011

Drug Info

Phase 1

Solid tumour/cancer

[19]

ALB-109564(a)

Drug Info

Phase 1

Solid tumour/cancer

[20]

CKD-516

Drug Info

Phase 1

Solid tumour/cancer

[21]

DAVLB-HYDRAZIDE

Drug Info

Phase 1

Solid tumour/cancer

[22]

NSC-639829

Drug Info

Phase 1

Solid tumour/cancer

[23]

Simotaxel

Drug Info

Phase 1

Solid tumour/cancer

[24]

STA-5312

Drug Info

Phase 1

Solid tumour/cancer

[25]

Tasidotin hydrochloride

Drug Info

Phase 1

Solid tumour/cancer

[26]

Discontinued Drug(s)

[+] 5 Discontinued Drugs

CEMADOTIN HYDROCHLORIDE

Drug Info

Discontinued in Phase 2

Solid tumour/cancer

[27]

Epothilone D

Drug Info

Discontinued in Phase 2

Breast cancer

[28]

RHIZOXIN

Drug Info

Discontinued in Phase 2

Breast cancer

[29]

S-12363

Drug Info

Discontinued in Phase 2

Solid tumour/cancer

[30]

Denibulin

Drug Info

Discontinued in Phase 1

Solid tumour/cancer

[31]

Preclinical Drug(s)

[+] 1 Preclinical Drugs

KOS-1803

Drug Info

Preclinical

Solid tumour/cancer

[32]

Mode of Action

[+] 3 Modes of Action

Binder

[+] 4 Binder drugs

Albendazole

Drug Info

[33]

Mebendazole

Drug Info

[33]

Vindesine

Drug Info

[1], [36]

Tasidotin hydrochloride

Drug Info

[55]

Modulator

[+] 17 Modulator drugs

Taxol

Drug Info

[34]

Vincristine

Drug Info

[35]

Plinabulin

Drug Info

[37]

ABT-751

Drug Info

[39]

BNC-105

Drug Info

[40]

Verubulin

Drug Info

[44]

1069C

Drug Info

[4], [47]

ABI-011

Drug Info

[48]

ALB-109564(a)

Drug Info

[49]

DAVLB-HYDRAZIDE

Drug Info

[4], [51]

NSC-639829

Drug Info

[4], [52]

CEMADOTIN HYDROCHLORIDE

Drug Info

[4], [56]

S-12363

Drug Info

[59]

APH-0911

Drug Info

[53]

ARC-200

Drug Info

[53]

IDN-5390

Drug Info

[53]

XN-0502

Drug Info

[53]

Inhibitor

[+] 52 Inhibitor drugs

Batabulin

Drug Info

[38]

DOLASTATIN-10

Drug Info

[41]

Lexibulin

Drug Info

[42]

T-607

Drug Info

[43]

ZD-6126

Drug Info

[45]

BAL-101553

Drug Info

[46]

CKD-516

Drug Info

[50]

Simotaxel

Drug Info

[53]

STA-5312

Drug Info

[4], [54]

Epothilone D

Drug Info

[57]

RHIZOXIN

Drug Info

[58]

Denibulin

Drug Info

[51]

KOS-1803

Drug Info

[53]

2'-amino-3,4,4',5-tetramethoxy-(Z)-stillbene

Drug Info

[60]

2,3'-diamino-3,4,4',5-tetramethoxy-(Z)-stillbene

Drug Info

[60]

2-(3-Chloro-phenyl)-1H-[1,8]naphthyridin-4-one

Drug Info

[61]

2-(4-Methoxy-phenyl)-1H-indole-3-carbaldehyde

Drug Info

[62]

2-amino-3,4',5-trimethoxy-(Z)-stillbene

Drug Info

[60]

2-Furan-2-yl-7-methyl-1H-[1,8]naphthyridin-4-one

Drug Info

[63]

2-m-Tolyl-1H-[1,8]naphthyridin-4-one

Drug Info

[61]

2-Methoxy-5-(3,4,5-trimethoxy-benzyl)-phenol

Drug Info

[64]

2-Methoxy-5-(3,4,5-trimethoxy-phenoxy)-phenol

Drug Info

[65]

2-Methoxy-5-(5,6,7-trimethoxy-indan-1-yl)-phenol

Drug Info

[66]

2-Naphthalen-1-yl-1H-[1,8]naphthyridin-4-one

Drug Info

[61]

2-Naphthalen-2-yl-1H-[1,8]naphthyridin-4-one

Drug Info

[61]

3,4',5-trimethoxy-(Z)-stilbene

Drug Info

[60]

3,4,4',5-tetramethoxy-(Z)-stilbene

Drug Info

[60]

3-bromo-4,4',5-trimethoxy-(Z)-stilbene

Drug Info

[60]

5,7-Dimethyl-2-m-tolyl-1H-[1,8]naphthyridin-4-one

Drug Info

[61]

5-Methyl-2-m-tolyl-1H-[1,8]naphthyridin-4-one

Drug Info

[61]

6-ile-ustiloxin

Drug Info

[41]

6-Methyl-2-m-tolyl-1H-[1,8]naphthyridin-4-one

Drug Info

[61]

7-Methyl-2-m-tolyl-1H-[1,8]naphthyridin-4-one

Drug Info

[61]

CENTAUREIDIN

Drug Info

[67]

COLCHINOL

Drug Info

[68]

COMBETASTATIN

Drug Info

[69]

GNF-PF-117

Drug Info

[70]

Isopropyl 3-(phenylthio)-1H-indole-2-carboxylate

Drug Info

[71]

MR-22388

Drug Info

[72]

MYOSEVERIN

Drug Info

[73]

N-(4-(3-(pyridin-2-yl)acryloyl)phenyl)acetamide

Drug Info

[74]

NSC-106970

Drug Info

[67]

NSC-664171

Drug Info

[75]

NSC-679036

Drug Info

[61]

ON-24160

Drug Info

[53]

PHENSTATIN

Drug Info

[76]

RTA-301

Drug Info

[53]

Thiocolchicine

Drug Info

[77]

TL-1892

Drug Info

[53]

USTILOXIN A

Drug Info

[41]

Ustiloxin D

Drug Info

[41]

Ustiloxin F

Drug Info

[41]

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 Affiliated Biological Pathways

Top

KEGG Pathway

[+] 3 KEGG Pathways

Phagosome

Gap junction

Pathogenic Escherichia coli infection

NetPath Pathway

[+] 3 NetPath Pathways

FSH Signaling Pathway

TCR Signaling Pathway

EGFR1 Signaling Pathway

Panther Pathway

[+] 2 Panther Pathways

Cytoskeletal regulation by Rho GTPase

Huntington disease

Reactome

[+] 5 Reactome Pathways

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

[+] 3 WikiPathways

Parkin-Ubiquitin Proteasomal System pathway

Pathogenic Escherichia coli infection

Mitotic G2-G2/M phases

Target-Related Models and Studies

Top

Target Validation

Target Validation Info

References

Top

REF 1

Antiproliferating 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 2

Opportunities and challenges in antiparasitic drug discovery. Nat Rev Drug Discov. 2005 Sep;4(9):727-40.

REF 3

Emerging drugs for irritable bowel syndrome. Expert Opin Emerg Drugs. 2006 May;11(2):293-313.

REF 4

Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015

REF 5

URL: 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 6

Vinflunine, a novel microtubule inhibitor, suppresses calmodulin interaction with the microtubule-associated protein STOP. Biochemistry. 2007 Dec 25;46(51):14899-906.

REF 7

Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.

REF 8

Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)

REF 9

ClinicalTrials.gov (NCT00057382) T138067 Versus Doxorubicin in Chemotherapy-Naive, Unresectable, Hepatocellular Carcinoma Patients. U.S. National Institutes of Health.

REF 10

ClinicalTrials.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 11

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800021025)

REF 12

ClinicalTrials.gov (NCT00003677) Dolastatin 10 in Treating Patients With Metastatic Pancreatic Cancer. U.S. National Institutes of Health.

REF 13

ClinicalTrials.gov (NCT00664378) Efficacy Study of CYT997 in Multiple Myeloma. U.S. National Institutes of Health.

REF 14

ClinicalTrials.gov (NCT00054249) T900607 in Treating Patients With Gastroesophageal Junction Cancer. U.S. National Institutes of Health.

REF 15

ClinicalTrials.gov (NCT01285414) Verubulin, Radiation Therapy, and Temozolomide to Treat Patients With Newly Diagnosed Glioblastoma Multiforme. U.S. National Institutes of Health.

REF 16

ClinicalTrials.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 17

ClinicalTrials.gov (NCT02490800) Phase 1/2a Study of Oral BAL101553 in Adult Patients With Solid Tumors.

REF 18

Phase 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 19

ClinicalTrials.gov (NCT01163071) A Phase 1 Trial of ABI-011 in Patients With Advanced Solid Tumors or Lymphomas. U.S. National Institutes of Health.

REF 20

ClinicalTrials.gov (NCT00724100) A Trial of ALB 109564(a) in Subjects With Advanced Solid Tumors. U.S. National Institutes of Health.

REF 21

ClinicalTrials.gov (NCT01560325) Safety Study of Increasing Doses of CKD-516 in Patients With Advanced Solid Cancers. U.S. National Institutes of Health.

REF 22

The 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 23

Phase 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 24

ClinicalTrials.gov (NCT00277836) Study Evaluating MST-997 in Advanced Malignant Solid Tumors. U.S. National Institutes of Health.

REF 25

ClinicalTrials.gov (NCT00276913) A Phase I Study of STA-5312 in Subjects With Advanced or Metastatic Solid Tumors. U.S. National Institutes of Health.

REF 26

Phase 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 27

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800006853)

REF 28

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800015773)

REF 29

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800001808)

REF 30

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000879)

REF 31

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800022182)

REF 32

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800024256)

REF 33

Flubendazole interferes with a wide spectrum of cell homeostatic mechanisms in Echinococcus granulosus protoscoleces. Parasitol Int. 2009 Sep;58(3):270-7.

REF 34

Paclitaxel directly binds to Bcl-2 and functionally mimics activity of Nur77. Cancer Res. 2009 Sep 1;69(17):6906-14.

REF 35

Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.

REF 36

Gene 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 37

NPI-2358 is a tubulin-depolymerizing agent: in-vitro evidence for activity as a tumor vascular-disrupting agent. Anticancer Drugs. 2006 Jan;17(1):25-31.

REF 38

Hydrophilic, 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.

REF 39

Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.

REF 40

The vascular disrupting agent BNC105 potentiates the efficacy of VEGF and mTOR inhibitors in renal and breast cancer.Cancer Biol Ther.2014;15(11):1552-60.

REF 41

Total synthesis and biological evaluation of ustiloxin natural products and two analogs. Bioorg Med Chem Lett. 2006 Sep 15;16(18):4804-7.

REF 42

National Cancer Institute Drug Dictionary (drug id 598799).

REF 43

Nucleophilic reactions of N-ethoxycarbonyliminopyridinium ylide with alpha,beta-unsaturated carbonyl compounds. Volume 28, Issue 6, 1972, Pages 1469-1476.

REF 44

Effects of the tumor-vasculature-disrupting agent verubulin and two heteroaryl analogues on cancer cells, endothelial cells, and blood vessels.ChemMedChem.2014 Apr;9(4):847-54.

REF 45

Phase 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 46

Initial 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 47

Patent WO2005108424 A1.

REF 48

Company report (Indena)

REF 49

2010 ASCO Annual Meeting

REF 50

CKD-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 51

An Overview of Tubulin Inhibitors That Interact with the Colchicine Binding Site. Pharm Res. 2012 November; 29(11): 2943-2971.

REF 52

Solubilization of NSC-639829. Int J Pharm. 2001 Aug 28;225(1-2):41-7.

REF 53

REF 54

Conjugated indole-imidazole derivatives displaying cytotoxicity against multidrug resistant cancer cell lines. Bioorganic & Medicinal Chemistry Letters. 11/2006; 16(19):5164-8.

REF 55

Intracellular activation and deactivation of tasidotin, an analog of dolastatin 15: correlation with cytotoxicity. Mol Pharmacol. 2009 Jan;75(1):218-26.

REF 56

Suppression of microtubule dynamics by binding of cemadotin to tubulin: possible mechanism for its antitumor action. Biochemistry. 1998 Dec 15;37(50):17571-8.

REF 57

How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.

REF 58

Tubulin polymerization inhibitors with a fluorinated phthalimide skeleton derived from thalidomide. Bioorg Med Chem Lett. 2006 Sep 15;16(18):4748-51.

REF 59

Microtubule assembly protects the region 28-38 of the beta- tubulin subunit. Article first published online: 4 FEB 2005.

REF 60

2-amino and 2'-aminocombretastatin derivatives as potent antimitotic agents. J Med Chem. 2006 Oct 19;49(21):6412-5.

REF 61

Antitumor agents. 178. Synthesis and biological evaluation of substituted 2-aryl-1,8-naphthyridin-4(1H)-ones as antitumor agents that inhibit tubul... J Med Chem. 1997 Sep 12;40(19):3049-56.

REF 62

Methoxy-substituted 3-formyl-2-phenylindoles inhibit tubulin polymerization. J Med Chem. 1998 Dec 3;41(25):4965-72.

REF 63

Antitumor agents. 196. Substituted 2-thienyl-1,8-naphthyridin-4-ones: their synthesis, cytotoxicity, and inhibition of tubulin polymerization. J Med Chem. 1999 Oct 7;42(20):4081-7.

REF 64

Synthesis of alkoxy-substituted diaryl compounds and correlation of ring separation with inhibition of tubulin polymerization: differential enhance... J Med Chem. 1992 Mar 20;35(6):1058-67.

REF 65

Antimitotic and cell growth inhibitory properties of combretastatin A-4-like ethers. Bioorg Med Chem Lett. 2001 Jan 8;11(1):51-4.

REF 66

The synthesis and evaluation of temperature sensitive tubulin toxins. Bioorg Med Chem Lett. 1999 Feb 8;9(3):407-12.

REF 67

Structure-activity requirements for flavone cytotoxicity and binding to tubulin. J Med Chem. 1998 Jun 18;41(13):2333-8.

REF 68

Synthesis and structure-activity relationships of 1,2,4-triazoles as a novel class of potent tubulin polymerization inhibitors. Bioorg Med Chem Lett. 2005 Dec 1;15(23):5154-9.

REF 69

Asymmetric synthesis of antimitotic combretadioxolane with potent antitumor activity against multi-drug resistant cells. Bioorg Med Chem Lett. 1998 Aug 4;8(15):1997-2000.

REF 70

Synthesis and cytotoxicity of 1,6,7,8-substituted 2-(4'-substituted phenyl)-4-quinolones and related compounds: identification as antimitotic agent... J Med Chem. 1993 Apr 30;36(9):1146-56.

REF 71

New arylthioindoles: potent inhibitors of tubulin polymerization. 2. Structure-activity relationships and molecular modeling studies. J Med Chem. 2006 Feb 9;49(3):947-54.

REF 72

Design, synthesis, and evaluation of novel thienopyrrolizinones as antitubulin agents. J Med Chem. 2004 Mar 11;47(6):1448-64.

REF 73

Synthesis and biological evaluation of myoseverin derivatives: microtubule assembly inhibitors. J Med Chem. 2001 Dec 20;44(26):4497-500.

REF 74

Design and biological evaluation of novel tubulin inhibitors as antimitotic agents using a pharmacophore binding model with tubulin. J Med Chem. 2006 Sep 21;49(19):5664-70.

REF 75

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 a... J Med Chem. 1998 Mar 26;41(7):1155-62.

REF 76

Antineoplastic agents. 465. Structural modification of resveratrol: sodium resverastatin phosphate. J Med Chem. 2002 Jun 6;45(12):2534-42.

REF 77

Antitumor agents. 139. Synthesis and biological evaluation of thiocolchicine analogs 5,6-dihydro-6(S)-(acyloxy)- and 5,6-dihydro-6(S)-[(aroyloxy)me... J Med Chem. 1993 Mar 5;36(5):544-51.

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