Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTML2WA)

DTT Name Tubulin (TUB)
Synonyms Human tubulin
Gene Name TUB
DTT Type
Successful target
 [1]
UniProt ID
NOUNIPROTAC
TTD ID
T43189
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.

Molecular Interaction Atlas (MIA) of This DTT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DTT
6 Approved Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
Cabazitaxel DMPAZHC Breast cancer 2C60-2C65 Approved [1]
Colchicine DM2POTE Acute gout flare FA25.0 Approved [2]
Docetaxel DMDI269 Advanced cancer 2A00-2F9Z Approved [3]
Eribulin DM1DX4Q Breast cancer 2C60-2C65 Approved [1]
Ixabepilone DM2OZ3G Breast cancer 2C60-2C65 Approved [1]
Vinorelbine DMVXFYE Advanced cancer 2A00-2F9Z Approved [4]
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⏷ Show the Full List of 6 Approved Drug(s)
12 Clinical Trial Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
Epothilon DMITJRU Ovarian cancer 2C73 Phase 3 [5]
BMS-184476 DMDPLEM Solid tumour/cancer 2A00-2F9Z Phase 2 [6]
BMS-188797 DML1CK2 Solid tumour/cancer 2A00-2F9Z Phase 2 [7]
BMS-275183 DMQL3VS Solid tumour/cancer 2A00-2F9Z Phase 2 [8]
CRYPTOPHYCIN 52 DM16IMT Solid tumour/cancer 2A00-2F9Z Phase 2 [9]
DOLASTATIN-10 DMDUV1S Solid tumour/cancer 2A00-2F9Z Phase 2 [10]
Indibulin DM6OFJ8 Advanced sarcoma 2A60-2C35 Phase 2 [11]
Milataxel DM50Z4U Solid tumour/cancer 2A00-2F9Z Phase 2 [12]
Soblidotin DMO4EYX Solid tumour/cancer 2A00-2F9Z Phase 2 [13]
BAL-101553 DMPFGL8 Solid tumour/cancer 2A00-2F9Z Phase 1/2 [14]
E 7974 DM3LOF1 Ovarian cancer 2C73 Phase 1 [5]
SDZ-LAV-694 DM8SINB Actinic keratosis EK90.0 Phase 1 [15]
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⏷ Show the Full List of 12 Clinical Trial Drug(s)
11 Discontinued Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
Epothilone B DMM5ZX6 Solid tumour/cancer 2A00-2F9Z Discontinued in Phase 3 [16]
Larotaxel DMCM239 Bladder cancer 2C94 Discontinued in Phase 3 [17]
ATX-201 DMWJ245 Actinic keratosis EK90.0 Discontinued in Phase 2 [18]
Cryptophycin DM73C4K N. A. N. A. Discontinued in Phase 2 [19]
ERBULOZOLE DM03I7V Solid tumour/cancer 2A00-2F9Z Discontinued in Phase 2 [20]
RHIZOXIN DMQ4IKZ Breast cancer 2C60-2C65 Discontinued in Phase 2 [21]
ABJ-879 DMJTIUP Solid tumour/cancer 2A00-2F9Z Discontinued in Phase 1 [22]
Discodermolide DMAR068 Immune System disease 4A01-4B41 Discontinued in Phase 1 [23]
FCE-28161 DMSFA7L Solid tumour/cancer 2A00-2F9Z Discontinued in Phase 1 [24]
TALTOBULIN DM1ZYCA Solid tumour/cancer 2A00-2F9Z Discontinued in Phase 1 [25]
21-AMINOEPOTHILONE B DMTH52F Solid tumour/cancer 2A00-2F9Z Terminated [27]
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⏷ Show the Full List of 11 Discontinued Drug(s)
1 Preclinical Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
ABI-013 DMQ0NU1 Solid tumour/cancer 2A00-2F9Z Preclinical [26]
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30 Investigative Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
2-(3-Chloro-phenyl)-1H-[1,8]naphthyridin-4-one DMK6CD9 Discovery agent N.A. Investigative [28]
2-(4-Methoxy-phenyl)-1H-indole-3-carbaldehyde DMTEQU8 Discovery agent N.A. Investigative [29]
2-Furan-2-yl-7-methyl-1H-[1,8]naphthyridin-4-one DMD8ZUH Discovery agent N.A. Investigative [30]
2-m-Tolyl-1H-[1,8]naphthyridin-4-one DM9ZVHJ Discovery agent N.A. Investigative [28]
2-Methoxy-5-(3,4,5-trimethoxy-benzyl)-phenol DMCGID6 Discovery agent N.A. Investigative [31]
2-Methoxy-5-(3,4,5-trimethoxy-phenoxy)-phenol DM6CAYV Discovery agent N.A. Investigative [32]
2-Methoxy-5-(5,6,7-trimethoxy-indan-1-yl)-phenol DM9LY0Z Discovery agent N.A. Investigative [33]
2-Naphthalen-1-yl-1H-[1,8]naphthyridin-4-one DMTSF6A Discovery agent N.A. Investigative [28]
2-Naphthalen-2-yl-1H-[1,8]naphthyridin-4-one DM12YH4 Discovery agent N.A. Investigative [28]
5,7-Dimethyl-2-m-tolyl-1H-[1,8]naphthyridin-4-one DMU618S Discovery agent N.A. Investigative [28]
5-Methyl-2-m-tolyl-1H-[1,8]naphthyridin-4-one DMH1IVN Discovery agent N.A. Investigative [28]
6-Methyl-2-m-tolyl-1H-[1,8]naphthyridin-4-one DMAQGZR Discovery agent N.A. Investigative [28]
7-Methyl-2-m-tolyl-1H-[1,8]naphthyridin-4-one DM7LGDC Discovery agent N.A. Investigative [28]
AL-209 DM7XHDC Central nervous system disease 8A04-8D87 Investigative [34]
AL-309 DM69X2Z Central nervous system disease 8A04-8D87 Investigative [34]
CENTAUREIDIN DMCLXO0 Discovery agent N.A. Investigative [35]
COLCHINOL DM326VN Discovery agent N.A. Investigative [36]
COMBETASTATIN DMIKD8X Discovery agent N.A. Investigative [37]
Eleutherobin DMMVZU0 Discovery agent N.A. Investigative [38]
GNF-PF-117 DM3INUK Discovery agent N.A. Investigative [39]
Isopropyl 3-(phenylthio)-1H-indole-2-carboxylate DMS8MBI Discovery agent N.A. Investigative [40]
MR-22388 DMIQ8GL Discovery agent N.A. Investigative [41]
MYOSEVERIN DMX1POR Discovery agent N.A. Investigative [42]
NSC-106970 DMHK0F6 Discovery agent N.A. Investigative [35]
NSC-664171 DMEF603 Discovery agent N.A. Investigative [43]
NSC-679036 DMPO2RU Discovery agent N.A. Investigative [28]
PHENSTATIN DMJ5GY7 Discovery agent N.A. Investigative [44]
Sarcodictyin A DMZR4FX Discovery agent N.A. Investigative [45]
Thiocolchicine DMJSKIP Discovery agent N.A. Investigative [46]
WR85915 DM9V0KP Discovery agent N.A. Investigative [47]
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⏷ Show the Full List of 30 Investigative Drug(s)

Molecular Expression Atlas (MEA) of This DTT

Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This DTT
Disease Name ICD 11 Studied Tissue p-value Fold-Change Z-score
Ovarian cancer 2C82 Ovarian tissue 7.94E-02 0.35 0.43
Breast cancer 2C82 Breast tissue 4.29E-15 0.3 0.59
Rheumatoid arthritis FA20 Synovial tissue 4.60E-02 0.71 1.23
Bladder cancer 2C82 Bladder tissue 4.53E-02 -0.12 -0.23
Sarcoma 2C82 Muscle tissue 2.73E-287 1.86 3.42
Lung cancer 2C82 Lung tissue 5.46E-09 0.28 0.72
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⏷ Show the Full List of DTT Expression Under 6 Diseases

References

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2 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.
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18 Clinical pipeline report, company report or official report of Kythera Biopharmaceuticals.
19 Single-walled tubulin ring polymers. Biopolymers. 2007 Aug 5-15;86(5-6):424-36.
20 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.
21 Tubulin polymerization inhibitors with a fluorinated phthalimide skeleton derived from thalidomide. Bioorg Med Chem Lett. 2006 Sep 15;16(18):4748-51.
22 Novel tubulin-targeting agents: anticancer activity and pharmacologic profile of epothilones and related analogues. Ann Oncol. 2007 Jul;18 Suppl 5:v9-15.
23 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.
24 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.
25 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.
26 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.
27 Tubulin-Interactive Natural Products as Anticancer Agents. Correction in: J Nat Prod. 2011 May 27; 74(5): 1352.
28 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.
29 Methoxy-substituted 3-formyl-2-phenylindoles inhibit tubulin polymerization. J Med Chem. 1998 Dec 3;41(25):4965-72.
30 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.
31 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.
32 Antimitotic and cell growth inhibitory properties of combretastatin A-4-like ethers. Bioorg Med Chem Lett. 2001 Jan 8;11(1):51-4.
33 The synthesis and evaluation of temperature sensitive tubulin toxins. Bioorg Med Chem Lett. 1999 Feb 8;9(3):407-12.
34 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.
35 Structure-activity requirements for flavone cytotoxicity and binding to tubulin. J Med Chem. 1998 Jun 18;41(13):2333-8.
36 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.
37 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.
38 Eleutherobin, a novel cytotoxic agent that induces tubulin polymerization, is similar to paclitaxel (Taxol). Cancer Res. 1998 Mar 15;58(6):1111-5.
39 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.
40 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.
41 Design, synthesis, and evaluation of novel thienopyrrolizinones as antitubulin agents. J Med Chem. 2004 Mar 11;47(6):1448-64.
42 Synthesis and biological evaluation of myoseverin derivatives: microtubule assembly inhibitors. J Med Chem. 2001 Dec 20;44(26):4497-500.
43 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.
44 Antineoplastic agents. 465. Structural modification of resveratrol: sodium resverastatin phosphate. J Med Chem. 2002 Jun 6;45(12):2534-42.
45 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.
46 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.
47 Cellular effects of leishmanial tubulin inhibitors on L. donovani. Mol Biochem Parasitol. 2000 Oct;110(2):223-36.