Payload Information
General Information of This Payload
| Payload ID | PAY0PCTOE |
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| Name | Tubulysin |
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| Synonyms |
TUBULYSIN; 1943604-24-7; CHEMBL1288708; EX-A5466A; DLKUYSQUHXBYPB-NSSHGSRYSA-N; AKOS040740948; HY-128914; CS-0102166
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| Target | Microtubule (MT) | |||||
| Structure |
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| Formula | C44H67N5O9S |
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| 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 |
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| 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
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| InChIKey |
DLKUYSQUHXBYPB-NSSHGSRYSA-N
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| 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
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| Pharmaceutical Properties | Molecule Weight |
842.1 |
Polar area |
213 |
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Complexity |
1390 |
xlogp Value |
5.4 |
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Heavy Count |
59 |
Rot Bonds |
24 |
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Hbond acc |
12 |
Hbond Donor |
3 |
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The activity data of This Payload
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 1/2 (discontinued)]
Identified from the Human Clinical Data
| Experiment 1 Reporting the Activity Date of This ADC | [3] | ||||
| Efficacy Data | Objective Response Rate (ORR) |
2.00
6.00 4.00 9.00 20.00 23.00 % |
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| 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).
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| 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.
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| 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.
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| 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.
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| 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.
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| 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.
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| Experiment 4 Reporting the Activity Date of This ADC | [6] | ||||
| Efficacy Data | Objective Response Rate (ORR) |
9%
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| Patients Enrolled |
Eligible participants (≥18 years, ECOG 0-1) must have mesothelin-positive measurable tumors (pancreatic/ovarian/gastric/NSCLC/mesothelioma) and ≥3-month life expectancy. Exclusions cover brain metastases, active/hepatitis infections, major surgery (<1 month), uncontrolled cardiac/liver/bone marrow dysfunction, or hypersensitivity to mesothelin antibodies/tubulysin/nivolumab-related agents.
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| Related Clinical Trial | |||||
| NCT Number | NCT02341625 | Phase Status | PHASE1|||PHASE2 | ||
| Clinical Description |
A Phase I/IIa Study of BMS-986148, a Mesothelin Directed Antibody Drug Conjugate, in Subjects With Select Advanced Solid Tumors
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| Primary Endpoint |
Safety outcomes include adverse events (AEs, SAEs, discontinuations, deaths) and laboratory toxicity shifts (hematology/chemistry) from baseline to 100 days post-treatment (≤6 months), analyzed by NCT CTCAE v4.03 criteria and grouped by dose/regimen.
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| Other Endpoint |
Pharmacokinetics (Cmax, Tmax, Ctau, Ctrough, AUC (0-t), AUC[TAU]) are assessed during Cycle 1, with arithmetic %CV reported. Efficacy endpoints (up to 58 months) include best overall response (CR/PR/SD/PD), ORR, duration of response (DoR), progression-free survival (PFS), and PFS rates (4-12 months), stratified by tumor type (mesothelioma, pancreatic, ovarian, NSCLC, gastric). QTcF interval changes and ADA status are also evaluated by dose/regimen.
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| Experiment 5 Reporting the Activity Date of This ADC | [7] | ||||
| Patients Enrolled |
Eligible participants must have advanced/metastatic mesothelin-expressing solid tumors, progression/intolerance to standard therapy, measurable disease per RECIST, and ECOG 0-1. Exclusions include brain metastases, uncontrolled cardiovascular disease, eye/peripheral neuropathy, hepatitis B/C infection, or other protocol-specified conditions.
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| Administration Dosage |
Specified dose on specified days
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| Related Clinical Trial | |||||
| NCT Number | NCT02884726 | Phase Status | PHASE1 | ||
| Clinical Description |
A Phase 1 Study of the Safety and Tolerability of BMS 986148 in Subjects With Advanced and/or Metastatic Solid Tumors
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| Primary Endpoint |
Safety analysis covers adverse events (AEs/SAEs), including discontinuations and deaths, from Day 1 to 30 days post-treatment, with grading and laboratory toxicity shifts from baseline as key metrics for participant safety assessment.
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| Other Endpoint |
Pharmacokinetic parameters (Cmax, Tmax, AUC (0-T), AUC (TAU), Ctrough, etc.) and accumulation indices (AI) are evaluated from Day 1 to 84, alongside tumor response based on RECIST criteria post-BMS-986148 treatment to assess drug exposure and efficacy.
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BMS-986183 [Phase 1/2 (discontinued)]
Identified from the Human Clinical Data
| Experiment 1 Reporting the Activity Date of This ADC | [8] | ||||
| Patients Enrolled |
Key inclusion criteria require advanced unresectable hepatocellular carcinoma (histologically confirmed) with Child-Pugh class A, ECOG 0-1, and contraception use. Exclusions cover prior liver transplant, uncontrolled portal hypertension, CNS metastases, active HBV/HCV/HDV/HIV co-infections, recent cardiovascular events, additional malignancies within 2 years, >2 prior systemic therapies (Part 2 restrictions), concurrent anticoagulation, recent radiotherapy, major allergies, and protocol-specified contraindications. Full eligibility details are available via BMSStudyConnect.com.
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| Related Clinical Trial | |||||
| NCT Number | NCT02828124 | Phase Status | PHASE1|||PHASE2 | ||
| Clinical Description |
A Phase 1/2 Study of BMS-986183 in Subjects With Advanced Hepatocellular Carcinoma
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| Primary Endpoint |
The study evaluates the safety profile of the treatment by monitoring the incidence and severity of adverse events (AEs), serious adverse events (SAEs), AEs leading to discontinuation or death, and laboratory toxicity grade shifts over a 24-month period.
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| Other Endpoint |
Efficacy assessments include Best Overall Response (BOR, requiring confirmation scan), Overall Response Rate (ORR), Duration of Response (DoR), Progression-Free Survival (PFS), and PFS rates at predefined intervals (12, 24, 36 weeks). Pharmacokinetic analysis focuses on Cmax, Tmax, AUC (0-T and TAU), Ctrough, CLT, Vss, Vz, accumulation indices (AI_Cmax, AI_Ctau, AI_AUC (TAU)), Css,avg, and T-HALF for BMS-986183 components (total antibody, active ADC, tubulysin) as monotherapy and with nivolumab. Additional endpoints include QTcF changes from baseline and anti-drug antibody (ADA) incidence.
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References