Payload Information

General Information of This Payload
Payload ID
PAY0PCTOE
Name
Tubulysin
Synonyms
TUBULYSIN; 1943604-24-7; CHEMBL1288708; EX-A5466A; DLKUYSQUHXBYPB-NSSHGSRYSA-N; AKOS040740948; HY-128914; CS-0102166
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Target(s) Microtubule (MT)
 Target Info 
Structure
Formula
C44H67N5O9S
Isosmiles
CC[C@H](C)[C@@H](C(=O)N(COC(=O)CC(C)C)[C@H](C[C@H](C1=NC(=CS1)C(=O)N[C@@H](CC2=CC=C(C=C2)C)C[C@H](C)C(=O)O)OC(=O)C)C(C)C)NC(=O)[C@H]3CCCCN3C
PubChem CID
52945681
InChI
InChI=1S/C44H67N5O9S/c1-11-29(7)39(47-41(53)35-14-12-13-19-48(35)10)43(54)49(25-57-38(51)20-26(2)3)36(27(4)5)23-37(58-31(9)50)42-46-34(24-59-42)40(52)45-33(21-30(8)44(55)56)22-32-17-15-28(6)16-18-32/h15-18,24,26-27,29-30,33,35-37,39H,11-14,19-23,25H2,1-10H3,(H,45,52)(H,47,53)(H,55,56)/t29-,30-,33+,35+,36+,37+,39-/m0/s1
InChIKey
DLKUYSQUHXBYPB-NSSHGSRYSA-N
IUPAC Name
(2S,4R)-4-[[2-[(1R,3R)-1-acetyloxy-4-methyl-3-[3-methylbutanoyloxymethyl-[(2S,3S)-3-methyl-2-[[(2R)-1-methylpiperidine-2-carbonyl]amino]pentanoyl]amino]pentyl]-1,3-thiazole-4-carbonyl]amino]-2-methyl-5-(4-methylphenyl)pentanoic acid
Pharmaceutical Properties
Molecule Weight
842.1
Polar area
213
Complexity
1390
xlogp Value
5.4
Heavy Count
59
Rot Bonds
24
Hbond acc
12
Hbond Donor
3
The activity data of This Payload
Standard Type Value Units Cell line Disease Model Cell line ID Reference
Half Maximal Inhibitory Concentration (IC50) 2.2 nM
A2780 cells
Ovarian endometrioid adenocarcinoma
CVCL_0134 
[1]
Half Maximal Inhibitory Concentration (IC50) 2.5 nM
LNCaP cells
Prostate carcinoma
CVCL_0395 
[2]
Each Antibody-drug Conjugate Related to This Payload
Full Information of The Activity Data of The ADC(s) Related to This Payload
BMS-986148 [Phase 2]
 ADC Info 
Identified from the Human Clinical Data
Click To Hide/Show 3 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [3]
Efficacy Data Objective Response Rate (ORR)
2.00% (All escalation, BMS-986148 monotherapy)
6.00% (All expansion, BMS-986148 monotherapy)
4.00% (Mesothelioma expansion, BMS-986148 monotherapy)
9.00% (Ovarian expansion)
20.00% (All, BMS-986148 + nivolumab)
23.00% (Mesothelioma, BMS-986148 + nivolumab)
Patients Enrolled
Pleural or peritoneal mesothelioma (except sarcomatoid mesothelioma), ovarian cancer (except mucinous carcinoma), pancreatic cancer, gastric cancer, or non-small cell lung cancer (adenocarcinoma only).
Administration Dosage
BMS-986148 monotherapy (0.1-1.6 mg/kg intravenously (i.v.) every 3 weeks or 0.4 or 0.6 mg/kg i.v. once weekly; n = 96) or BMS-986148 0.8 mg/kg + nivolumab 360 mg i.v. every 3 weeks (n = 30). The primary endpoint was safety and tolerability.
Related Clinical Trial
NCT Number NCT02341625  Phase Status Phase 1/2a
Clinical Description
A phase 1/2a study of BMS-986148, a mesothelin directed antibody drug conjugate, in subjects with select advanced solid tumors.
Primary Endpoint
The MTD and the recommended dose for the part 2 monotherapy expansion is BMS-986148 1.20 mg/kg every 3 weeks dose level. The MTD in the combination expansion cohort is BMS-986148 0.80 mg/kg + nivolumab 360 mg every 3 weeks.
Experiment 2 Reporting the Activity Date of This ADC [4]
Related Clinical Trial
NCT Number NCT02341625  Phase Status Phase 1/2
Clinical Description
A phase 1/2a study of BMS-986148, a mesothelin directed antibody drug conjugate, in subjects with select advanced solid tumors.
Experiment 3 Reporting the Activity Date of This ADC [5]
Related Clinical Trial
NCT Number NCT02884726  Phase Status Phase 1
Clinical Description
A phase 1 study of the safety and tolerability of BMS 986148 in subjects with advanced and/or metastatic solid tumors.
References
Ref 1 Recent advances in the chemistry and biology of new generation taxoids. J Nat Prod. 2009 Mar 27;72(3):554-65. doi: 10.1021/np8006556.
Ref 2 Synthesis and biological analysis of prostate-specific membrane antigen-targeted anticancer prodrugs. J Med Chem. 2010 Nov 11;53(21):7767-77. doi: 10.1021/jm100729b.
Ref 3 Phase I/IIa Trial of BMS-986148, an Anti-mesothelin Antibody-drug Conjugate, Alone or in Combination with Nivolumab in Patients with Advanced Solid Tumors. Clin Cancer Res. 2022 Jan 1;28(1):95-105.
Ref 4 A Phase I/IIa Study of BMS-986148, a Mesothelin Directed Antibody Drug Conjugate, in Subjects With Select Advanced Solid Tumors, NCT02341625
Ref 5 A Phase 1 Study of the Safety and Tolerability of BMS 986148 in Subjects With Advanced and/or Metastatic Solid Tumors, NCT02884726

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