| Size | Price | Stock | Qty |
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| 2mg |
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| 5mg |
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| 10mg |
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| 25mg |
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| Other Sizes |
| Targets |
Auristatin
Val-Cit-PAB-MMAE targets cathepsin B, a cysteine protease that cleaves the Val-Cit dipeptide linker. Upon cleavage, the PAB spacer undergoes self-immolation, releasing the active MMAE payload. MMAE targets tubulin, inhibiting microtubule polymerization and causing cell cycle arrest and apoptosis in cancer cells. |
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| ln Vitro |
Val-Cit-PAB-MMAE itself is not directly active; its activity depends on cleavage by cathepsin B to release MMAE. MMAE is a potent antimitotic agent that inhibits tubulin polymerization, leading to cell cycle arrest at the G₂/M phase and apoptosis. The Val-Cit-PAB linker ensures that MMAE is selectively released in cathepsin B-overexpressing cancer cells.
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| ln Vivo |
Val-Cit-PAB-MMAE is used in ADCs that have been evaluated in vivo in animal models and clinical trials. The ADCs target tumor-associated antigens, delivering MMAE selectively to tumor cells. This targeted approach enhances the therapeutic index of MMAE, reducing systemic toxicity while maintaining potent antitumor activity.
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| Enzyme Assay |
In vitro non-cell assays for Val-Cit-PAB-MMAE typically involve measuring cathepsin B-mediated cleavage of the linker. The compound is incubated with purified cathepsin B, and the release of MMAE or the PAB-MMAE intermediate is measured by HPLC or LC-MS/MS.
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| Cell Assay |
In vitro cell-based assays for Val-Cit-PAB-MMAE use cancer cell lines that express cathepsin B and the target antigen (for ADC studies). Cells are treated with the ADC containing Val-Cit-PAB-MMAE, and parameters assessed include cell viability (MTT or CCK-8 assays), cell cycle analysis, apoptosis (Annexin V/PI staining), and MMAE release (by LC-MS/MS).
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| Animal Protocol |
In vivo animal studies for Val-Cit-PAB-MMAE employ xenograft mouse models using cancer cell lines expressing the target antigen. The ADC is administered intravenously, and parameters assessed include tumor growth inhibition, survival, MMAE concentrations in plasma and tissues, and evaluation of systemic toxicity.
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| ADME/Pharmacokinetics |
Val-Cit-PAB-MMAE has a molecular weight of approximately 1,317.6 g/mol (as the conjugate). The Val-Cit-PAB linker and MMAE payload are well characterized. The compound is used in ADC development and is typically stored under appropriate conditions as recommended by the manufacturer.
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| Toxicity/Toxicokinetics |
The toxicity of Val-Cit-PAB-MMAE is primarily associated with the MMAE payload. MMAE can cause peripheral neuropathy, myelosuppression, and other toxicities associated with antimitotic agents. The Val-Cit-PAB linker and PAB spacer are designed to minimize systemic toxicity by enabling selective release in tumor cells.
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| References | |
| Additional Infomation |
Val-Cit-Pab-MMAE is a peptide-drug conjugate used in antibody-drug conjugates (ADCs) for targeted cancer therapy. It consists of a Val-Cit dipeptide linker, a PAB spacer, and the potent antimitotic agent MMAE. The linker is cleaved by cathepsin B in tumor cells, releasing MMAE for targeted cell killing. Not approved as a standalone drug; used as a component in ADC development.
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| Molecular Formula |
C58H94N10O12
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|---|---|
| Molecular Weight |
1123.4268
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| Exact Mass |
1122.705
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| Elemental Analysis |
C, 62.01; H, 8.43; N, 12.47; O, 17.09
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| CAS # |
644981-35-1
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| Related CAS # |
Val-Cit-PAB-MMAE;644981-35-1
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| PubChem CID |
88914158
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| Appearance |
White to off-white solid powder
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| Density |
1.2±0.1 g/cm3
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| Boiling Point |
1211.9±65.0 °C at 760 mmHg
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| Flash Point |
686.7±34.3 °C
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| Vapour Pressure |
0.0±0.3 mmHg at 25°C
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| Index of Refraction |
1.552
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| LogP |
4.8
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| Hydrogen Bond Donor Count |
8
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| Hydrogen Bond Acceptor Count |
13
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| Rotatable Bond Count |
32
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| Heavy Atom Count |
80
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| Complexity |
1980
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| Defined Atom Stereocenter Count |
12
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| SMILES |
O(C([H])([H])[H])[C@]([H])([C@]([H])(C(N([H])[C@]([H])(C([H])([H])[H])[C@]([H])(C1C([H])=C([H])C([H])=C([H])C=1[H])O[H])=O)C([H])([H])[H])[C@]1([H])C([H])([H])C([H])([H])C([H])([H])N1C(C([H])([H])[C@]([H])([C@]([H])([C@@]([H])(C([H])([H])[H])C([H])([H])C([H])([H])[H])N(C([H])([H])[H])C([C@]([H])(C([H])(C([H])([H])[H])C([H])([H])[H])N([H])C([C@]([H])(C([H])(C([H])([H])[H])C([H])([H])[H])N(C(=O)OC([H])([H])C1C([H])=C([H])C(=C([H])C=1[H])N([H])C([C@]([H])(C([H])([H])C([H])([H])C([H])([H])N([H])C(N([H])[H])=O)N([H])C([C@]([H])(C([H])(C([H])([H])[H])C([H])([H])[H])N([H])[H])=O)=O)C([H])([H])[H])=O)=O)OC([H])([H])[H])=O
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| InChi Key |
WZEAGSMYTVSXQA-XZZQEHRXSA-N
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| InChi Code |
InChI=1S/C58H94N10O12 c1-15-36(8)49(44(78-13)31-45(69)68-30-20-24-43(68)51(79-14)37(9)52(71)62-38(10)50(70)40-21-17-16-18-22-40)66(11)56(75)47(34(4)5)65-55(74)48(35(6)7)67(12)58(77)80-32-39-25-27-41(28-26-39)63-53(72)42(23-19-29-61-57(60)76)64-54(73)46(59)33(2)3/h16-18,21-22,25-28,33-38,42-44,46-51,70H,15,19-20,23-24,29-32,59H2,1-14H3,(H,62,71)(H,63,72)(H,64,73)(H,65,74)(H3,60,61,76)/t36-,37+,38+,42-,43-,44+,46-,47-,48-,49-,50+,51+/m0/s1
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| Chemical Name |
[4-[[(2S)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-5-(carbamoylamino)pentanoyl]amino]phenyl]methyl N-[(2S)-1-[[(2S)-1-[[(3R,4S,5S)-1-[(2S)-2-[(1R,2R)-3-[[(1S,2R)-1-hydroxy-1-phenylpropan-2-yl]amino]-1-methoxy-2-methyl-3-oxopropyl]pyrrolidin-1-yl]-3-methoxy-5-methyl-1-oxoheptan-4-yl]-methylamino]-3-methyl-1-oxobutan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]-N-methylcarbamate
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| Synonyms |
Val-Cit-PAB-MMAE; MMAE ADC conjugate; N-PM-0008; N-PM 0008; N-PM0008; NPM-0008; NPM 0008; NPM0008;
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ≥ 110 mg/mL (~97.91 mM)
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| Solubility (In Vivo) |
10% DMSO+ 90% (20% SBE-β-CD in saline): ≥ 5.5 mg/mL (4.90 mM) (Please use freshly prepared in vivo formulations for optimal results.)
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| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.8901 mL | 4.4507 mL | 8.9013 mL | |
| 5 mM | 0.1780 mL | 0.8901 mL | 1.7803 mL | |
| 10 mM | 0.0890 mL | 0.4451 mL | 0.8901 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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