VcMMAE

• CAT Number: I004434
• CAS Number: 646502-53-6
• Molecular Formula: C68H105N11O15
• Molecular Weight: 1316.63
• Purity: ≥95%
• Target: Antibody-drug conjugate; Tubulin
• Solubility: DMSO: ≥ 54 mg/mL
• Storage: Room Temperature
• IUPAC Name: [4-[[(2S)-5-(carbamoylamino)-2-[[(2S)-2-[6-(2,5-dioxopyrrol-1-yl)hexanoylamino]-3-methylbutanoyl]amino]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
• InChI: InChI=1S/C68H105N11O15/c1-15-43(8)59(51(92-13)38-55(83)78-37-23-27-50(78)61(93-14)44(9)62(85)71-45(10)60(84)47-24-18-16-19-25-47)76(11)66(89)57(41(4)5)75-65(88)58(42(6)7)77(12)68(91)94-39-46-29-31-48(32-30-46)72-63(86)49(26-22-35-70-67(69)90)73-64(87)56(40(2)3)74-52(80)28-20-17-21-36-79-53(81)33-34-54(79)82/h16,18-19,24-25,29-34,40-45,49-51,56-61,84H,15,17,20-23,26-28,35-39H2,1-14H3,(H,71,85)(H,72,86)(H,73,87)(H,74,80)(H,75,88)(H3,69,70,90)/t43-,44+,45+,49-,50-,51+,56-,57-,58-,59-,60+,61+/m0/s1
• InChIKey: NLMBVBUNULOTNS-HOKPPMCLSA-N
• SMILES: CCC(C)C(C(CC(=O)N1CCCC1C(C(C)C(=O)NC(C)C(C2=CC=CC=C2)O)OC)OC)N(C)C(=O)C(C(C)C)NC(=O)C(C(C)C)N(C)C(=O)OCC3=CC=C(C=C3)NC(=O)C(CCCNC(=O)N)NC(=O)C(C(C)C)NC(=O)CCCCCN4C(=O)C=CC4=O

VcMMAE（Cat No.:I004434） is an antibody-drug conjugate (ADC) designed for potent antitumor activity. It utilizes monomethyl auristatin E (MMAE), an anti-mitotic agent, as its payload. MMAE is linked to the ADC through a lysosomally cleavable dipeptide, valine-citrulline (vc). This linker enables specific delivery of MMAE to tumor cells via antibody targeting. Once inside the tumor cells, the dipeptide linker is cleaved in the lysosomes, releasing MMAE and leading to its potent cytotoxic effects, ultimately resulting in tumor cell death. VcMMAE represents a promising approach in targeted cancer therapy using antibody-drug conjugates.

Reference

1:The HB22.7-vcMMAE antibody-drug conjugate has efficacy against non-Hodgkin lymphoma mouse xenografts with minimal systemic toxicity. Abuhay M, Kato J, Tuscano E, Barisone GA, Sidhu RS, O/’Donnell RT, Tuscano JM.Cancer Immunol Immunother. 2016 Oct;65(10):1169-75. doi: 10.1007/s00262-016-1873-y. Epub 2016 Aug 9. PMID: 27506529 2:Cathepsin B Cleavage of vcMMAE-Based Antibody-Drug Conjugate Is Not Drug Location or Monoclonal Antibody Carrier Specific. Gikanga B, Adeniji NS, Patapoff TW, Chih HW, Yi L.Bioconjug Chem. 2016 Apr 20;27(4):1040-9. doi: 10.1021/acs.bioconjchem.6b00055. Epub 2016 Mar 10. PMID: 26914498 3:Management of metastatic breast cancer with second-generation antibody-drug conjugates: focus on glembatumumab vedotin (CDX-011, CR011-vcMMAE). Vaklavas C, Forero A.BioDrugs. 2014 Jun;28(3):253-63. doi: 10.1007/s40259-014-0085-2. Review. PMID: 24496926 4:Pharmacologically enhanced expression of GPNMB increases the sensitivity of melanoma cells to the CR011-vcMMAE antibody-drug conjugate. Qian X, Mills E, Torgov M, LaRochelle WJ, Jeffers M.Mol Oncol. 2008 Jun;2(1):81-93. doi: 10.1016/j.molonc.2008.02.002. Epub 2008 Feb 16. PMID: 19383330 Free Article5:Potent antitumor activity of the anti-CD19 auristatin antibody drug conjugate hBU12-vcMMAE against rituximab-sensitive and -resistant lymphomas. Gerber HP, Kung-Sutherland M, Stone I, Morris-Tilden C, Miyamoto J, McCormick R, Alley SC, Okeley N, Hayes B, Hernandez-Ilizaliturri FJ, McDonagh CF, Carter PJ, Benjamin D, Grewal IS.Blood. 2009 Apr 30;113(18):4352-61. doi: 10.1182/blood-2008-09-179143. Epub 2009 Jan 15. PMID: 19147785 Free Article6:Treatment parameters modulating regression of human melanoma xenografts by an antibody-drug conjugate (CR011-vcMMAE) targeting GPNMB. Pollack VA, Alvarez E, Tse KF, Torgov MY, Xie S, Shenoy SG, MacDougall JR, Arrol S, Zhong H, Gerwien RW, Hahne WF, Senter PD, Jeffers ME, Lichenstein HS, LaRochelle WJ.Cancer Chemother Pharmacol. 2007 Aug;60(3):423-35. Epub 2007 Jun 1. PMID: 17541593 7:Secondary mAb–vcMMAE conjugates are highly sensitive reporters of antibody internalization via the lysosome pathway. Klussman K, Mixan BJ, Cerveny CG, Meyer DL, Senter PD, Wahl AF.Bioconjug Chem. 2004 Jul-Aug;15(4):765-73. PMID: 15264863 8:cAC10-vcMMAE, an anti-CD30-monomethyl auristatin E conjugate with potent and selective antitumor activity. Francisco JA, Cerveny CG, Meyer DL, Mixan BJ, Klussman K, Chace DF, Rejniak SX, Gordon KA, DeBlanc R, Toki BE, Law CL, Doronina SO, Siegall CB, Senter PD, Wahl AF.Blood. 2003 Aug 15;102(4):1458-65. Epub 2003 Apr 24. PMID: 12714494 Free Article