Target Information

Target General Information

Top

Target ID

T43189 (Former ID: TTDS00271)

Target Name

Tubulin (TUB)

Synonyms

Human tubulin

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Gene Name

NO-GeName

Target Type

Successful target

[1]

Disease

[+] 3 Target-related Diseases

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

Gout [ICD-11: FA25]

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. TUBB3 plays a critical role in proper axon guidance and mantainance.

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UniProt ID

NOUNIPROTAC

Drugs and Modes of Action

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Approved Drug(s)

[+] 6 Approved Drugs

Cabazitaxel

Drug Info

Approved

Breast cancer

[1], [2]

Colchicine

Drug Info

Approved

Acute gouty arthritis

[3], [4], [5]

Docetaxel

Drug Info

Approved

Solid tumour/cancer

[6], [7]

Eribulin

Drug Info

Approved

Breast cancer

[8], [1]

Ixabepilone

Drug Info

Approved

Breast cancer

[1], [9], [10]

Vinorelbine

Drug Info

Approved

Solid tumour/cancer

[11], [7]

Clinical Trial Drug(s)

[+] 12 Clinical Trial Drugs

Epothilon

Drug Info

Phase 3

Ovarian cancer

[12]

BMS-184476

Drug Info

Phase 2

Solid tumour/cancer

[13]

BMS-188797

Drug Info

Phase 2

Solid tumour/cancer

[14], [15]

BMS-275183

Drug Info

Phase 2

Solid tumour/cancer

[16]

CRYPTOPHYCIN 52

Drug Info

Phase 2

Solid tumour/cancer

[17]

DOLASTATIN-10

Drug Info

Phase 2

Solid tumour/cancer

[18]

Indibulin

Drug Info

Phase 2

Advanced sarcoma

[19]

Milataxel

Drug Info

Phase 2

Solid tumour/cancer

[20]

Soblidotin

Drug Info

Phase 2

Solid tumour/cancer

[21]

BAL-101553

Drug Info

Phase 1/2

Solid tumour/cancer

[22]

E 7974

Drug Info

Phase 1

Ovarian cancer

[12]

SDZ-LAV-694

Drug Info

Phase 1

Actinic keratosis

[23]

Discontinued Drug(s)

[+] 10 Discontinued Drugs

Epothilone B

Drug Info

Discontinued in Phase 3

Solid tumour/cancer

[24]

Larotaxel

Drug Info

Discontinued in Phase 3

Bladder cancer

[25]

ATX-201

Drug Info

Discontinued in Phase 2

Actinic keratosis

[26]

ERBULOZOLE

Drug Info

Discontinued in Phase 2

Solid tumour/cancer

[27]

RHIZOXIN

Drug Info

Discontinued in Phase 2

Breast cancer

[28]

ABJ-879

Drug Info

Discontinued in Phase 1

Solid tumour/cancer

[29]

Discodermolide

Drug Info

Discontinued in Phase 1

Immune System disease

[30]

FCE-28161

Drug Info

Discontinued in Phase 1

Solid tumour/cancer

[31]

TALTOBULIN

Drug Info

Discontinued in Phase 1

Solid tumour/cancer

[32]

21-AMINOEPOTHILONE B

Drug Info

Terminated

Solid tumour/cancer

[34]

Preclinical Drug(s)

[+] 1 Preclinical Drugs

ABI-013

Drug Info

Preclinical

Solid tumour/cancer

[33]

Mode of Action

[+] 5 Modes of Action

Inhibitor

[+] 45 Inhibitor drugs

Cabazitaxel

Drug Info

[1]

Docetaxel

Drug Info

[36]

Eribulin

Drug Info

[1]

Vinorelbine

Drug Info

[37]

BMS-184476

Drug Info

[4], [38]

BMS-188797

Drug Info

[4], [39]

BMS-275183

Drug Info

[40]

CRYPTOPHYCIN 52

Drug Info

[4], [17]

DOLASTATIN-10

Drug Info

[41]

Milataxel

Drug Info

[42]

BAL-101553

Drug Info

[44]

E 7974

Drug Info

[12]

SDZ-LAV-694

Drug Info

[4], [45]

Epothilone B

Drug Info

[46]

Larotaxel

Drug Info

[47]

ATX-201

Drug Info

[48]

RHIZOXIN

Drug Info

[51]

TALTOBULIN

Drug Info

[4], [55]

21-AMINOEPOTHILONE B

Drug Info

[4], [57]

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

Drug Info

[58]

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

Drug Info

[59]

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

Drug Info

[60]

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

Drug Info

[58]

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

Drug Info

[61]

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

Drug Info

[62]

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

Drug Info

[63]

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

Drug Info

[58]

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

Drug Info

[58]

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

Drug Info

[58]

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

Drug Info

[58]

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

Drug Info

[58]

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

Drug Info

[58]

CENTAUREIDIN

Drug Info

[65]

COLCHINOL

Drug Info

[66]

COMBETASTATIN

Drug Info

[67]

GNF-PF-117

Drug Info

[69]

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

Drug Info

[70]

MR-22388

Drug Info

[71]

MYOSEVERIN

Drug Info

[72]

NSC-106970

Drug Info

[65]

NSC-664171

Drug Info

[73]

NSC-679036

Drug Info

[58]

PHENSTATIN

Drug Info

[74]

Thiocolchicine

Drug Info

[76]

WR85915

Drug Info

[77]

Binder

[+] 1 Binder drugs

Colchicine

Drug Info

[35]

Stablizer

[+] 3 Stablizer drugs

Ixabepilone

Drug Info

[1]

Epothilon

Drug Info

[12]

Indibulin

Drug Info

[19]

Modulator

[+] 7 Modulator drugs

Soblidotin

Drug Info

[43]

ERBULOZOLE

Drug Info

[4], [50]

ABJ-879

Drug Info

[52]

Discodermolide

Drug Info

[53]

FCE-28161

Drug Info

[4], [54]

AL-209

Drug Info

[64]

AL-309

Drug Info

[64]

Inducer

[+] 3 Inducer drugs

Cryptophycin

Drug Info

[49]

Eleutherobin

Drug Info

[68]

Sarcodictyin A

Drug Info

[75]

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

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Co-Targets

Co-Targets Info

Target Regulators

Top

Target-regulating microRNAs

Target-regulating microRNAs Info

Target Profiles in Patients

Top

Target Expression
Profile (TEP)

Target Expression Profile Info

Target-Related Models and Studies

Top

Target Validation

Target Validation Info

References

Top

REF 1

Mullard A: 2010 FDA drug approvals. Nat Rev Drug Discov. 2011 Feb;10(2):82-5.

REF 2

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: 6798).

REF 3

REF 4

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

REF 5

FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (ANDA) 084279.

REF 6

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

REF 9

REF 10

2007 FDA drug approvals: a year of flux. Nat Rev Drug Discov. 2008 Feb;7(2):107-9.

REF 11

REF 12

Emerging drugs for ovarian cancer. Expert Opin Emerg Drugs. 2008 Sep;13(3):523-36.

REF 13

Phase 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.

REF 14

A 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 15

ClinicalTrials.gov (NCT00006086) BMS-188797 and Carboplatin in Treating Patients With Advanced Nonhematologic Cancer. U.S. National Institutes of Health.

REF 16

ClinicalTrials.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 17

Phase 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 18

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

REF 19

2011 Pipeline of ZioPharm.

REF 20

ClinicalTrials.gov (NCT00685204) An Efficacy Study of Milataxel (TL139) Administered Orally for Malignant Mesothelioma. U.S. National Institutes of Health.

REF 21

ClinicalTrials.gov (NCT00064220) Soblidotin in Treating Patients With Advanced or Metastatic Soft Tissue Sarcoma. U.S. National Institutes of Health.

REF 22

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

REF 23

Recent 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 24

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800005849)

REF 25

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800010227)

REF 26

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800026557)

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 800003227)

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 800001808)

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 800020424)

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 800008133)

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 800007669)

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 800019128)

REF 33

Clinical pipeline report, company report or official report of Celgene Corporation.

REF 34

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800017146)

REF 35

Vitamin 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 36

Docetaxel: a review of its use in metastatic breast cancer. Drugs. 2005;65(17):2513-31.

REF 37

Vinca alkaloid and MDR1. Gan To Kagaku Ryoho. 2008 Jul;35(7):1086-9.

REF 38

Phase 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 39

Phase 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 40

A 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 41

Synthesis and biological activity of chimeric structures derived from the cytotoxic natural compounds dolastatin 10 and dolastatin 15. J Med Chem. 1998 Apr 23;41(9):1524-30.

REF 42

J Clin Oncol 28, 2010 (suppl; abstr e13075).

REF 43

Antitumor activity of TZT-1027 (Soblidotin). Anticancer Res. 2006 May-Jun;26(3A):1973-81.

REF 44

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

REF 45

Recent 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 46

Emerging therapies for multiple myeloma. Expert Opin Emerg Drugs. 2009 Mar;14(1):99-127.

REF 47

Pharma & Vaccines. Product Development Pipeline. April 29 2009.

REF 48

Clinical pipeline report, company report or official report of Kythera Biopharmaceuticals.

REF 49

Single-walled tubulin ring polymers. Biopolymers. 2007 Aug 5-15;86(5-6):424-36.

REF 50

Influence 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 51

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

REF 52

Novel tubulin-targeting agents: anticancer activity and pharmacologic profile of epothilones and related analogues. Ann Oncol. 2007 Jul;18 Suppl 5:v9-15.

REF 53

The 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 54

CN 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 55

Absolute 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 56

Cardiovascular 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 57

Tubulin-Interactive Natural Products as Anticancer Agents. Correction in: J Nat Prod. 2011 May 27; 74(5): 1352.

REF 58

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 59

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

REF 60

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 61

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 62

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

REF 63

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

REF 64

Protection 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 65

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

REF 66

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 67

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 68

Eleutherobin, a novel cytotoxic agent that induces tubulin polymerization, is similar to paclitaxel (Taxol). Cancer Res. 1998 Mar 15;58(6):1111-5.

REF 69

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 70

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 71

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

REF 72

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

REF 73

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 74

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

REF 75

The 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 76

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.

REF 77

Cellular effects of leishmanial tubulin inhibitors on L. donovani. Mol Biochem Parasitol. 2000 Oct;110(2):223-36.

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