VcMMAE
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MedKoo CAT#: 407406

CAS#: 646502-53-6

Description: VcMMAE is a MMAE derivative with valine-citrulline (Vc) linker. VcMMAE can be used to make antibody drug conjugate. VcMMAE is a anti-mitotic agent, monomethyl auristatin E (MMAE), linked via the lysosomally cleavable dipeptide, valine-citrulline (vc). Monomethyl auristatin E (MMAE) is a synthetic antineoplastic agent. Because of its toxicity, it cannot be used as a drug itself; instead, it is linked to a monoclonal antibody (MAB) which directs it to the cancer cells. In International Nonproprietary Names for MMAE-MAB-conjugates, the name vedotin refers to MMAE plus its linking structure to the antibody. It is a potent antimitotic drug derived from peptides occurring in marine shell-less mollusc Dolabella auricularia called dolastatins which show potent activity in preclinical studies, both in vitro and in vivo, against a range of lymphomas, leukemia and solid tumors. These drugs show potency of up to 200 times that of vinblastine, another antimitotic drug used for Hodgkin lymphoma as well as other types of cancer


Price and Availability

Size
Price

5mg
USD 450
100mg
USD 1650
Size
Price

10mg
USD 750
500mg
USD 2950
Size
Price

50mg
USD 1250
1g
USD 4650

VcMMAE, purity > 98%, is in stock. The same day shipping out after order is received. Note: the estimated shipping out time for order > 10mg may be 2 months.


Chemical Structure

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Theoretical Analysis

MedKoo Cat#: 407406
Name: VcMMAE
CAS#: 646502-53-6
Chemical Formula: C68H105N11O15
Exact Mass: 1315.7792
Molecular Weight: 1316.65
Elemental Analysis: C, 62.03; H, 8.04; N, 11.70; O, 18.23


Synonym: VcMMAE; Vc-MMAE; MC-VC-PAB-MMAE; MMAE Vc linker, MMAE antibody conjugate

IUPAC/Chemical Name: 4-((S)-2-((S)-2-(6-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)hexanamido)-3-methylbutanamido)-5-ureidopentanamido)benzyl ((S)-1-(((S)-1-(((3R,4S,5S)-1-((S)-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)(methyl)amino)-3-methyl-1-oxobutan-2-yl)amino)-3-methyl-1-oxobutan-2-yl)(methyl)carbamate

InChi Key: NLMBVBUNULOTNS-HOKPPMCLSA-N

InChi Code: 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

SMILES Code: CC[C@@H]([C@H](N(C([C@@H](NC([C@@H](N(C(OCC1=CC=C(NC([C@@H](NC([C@@H](NC(CCCCCN2C(C=CC2=O)=O)=O)C(C)C)=O)CCCNC(N)=O)=O)C=C1)=O)C)C(C)C)=O)C(C)C)=O)C)[C@H](OC)CC(N3CCC[C@H]3[C@H](OC)[C@H](C(N[C@@H]([C@@H](O)C4=CC=CC=C4)C)=O)C)=O)C


Technical Data

Appearance:
White to off-white solid powder

Purity:
>98% (or refer to the Certificate of Analysis)

Safety Data Sheet (MSDS):

Shipping Condition:
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition:
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility:
Soluble in DMSO

Shelf Life:
>2 years if stored properly

Drug Formulation:
This drug may be formulated in DMSO

Stock Solution Storage:
0 - 4 C for short term (days to weeks), or -20 C for long term (months).

Harmonized System Code:
293490


References

1: Abuhay M, Kato J, Tuscano E, Barisone GA, Sidhu RS, O'Donnell RT, Tuscano JM. The HB22.7-vcMMAE antibody-drug conjugate has efficacy against non-Hodgkin lymphoma mouse xenografts with minimal systemic toxicity. Cancer Immunol Immunother. 2016 Oct;65(10):1169-75. doi: 10.1007/s00262-016-1873-y. PubMed PMID: 27506529.

2: 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. Treatment parameters modulating regression of human melanoma xenografts by an antibody-drug conjugate (CR011-vcMMAE) targeting GPNMB. Cancer Chemother Pharmacol. 2007 Aug;60(3):423-35. PubMed PMID: 17541593.

3: Qian X, Mills E, Torgov M, LaRochelle WJ, Jeffers M. Pharmacologically enhanced expression of GPNMB increases the sensitivity of melanoma cells to the CR011-vcMMAE antibody-drug conjugate. Mol Oncol. 2008 Jun;2(1):81-93. doi: 10.1016/j.molonc.2008.02.002. PubMed PMID: 19383330.

4: 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. Potent antitumor activity of the anti-CD19 auristatin antibody drug conjugate hBU12-vcMMAE against rituximab-sensitive and -resistant lymphomas. Blood. 2009 Apr 30;113(18):4352-61. doi: 10.1182/blood-2008-09-179143. PubMed PMID: 19147785.

5: Gikanga B, Adeniji NS, Patapoff TW, Chih HW, Yi L. Cathepsin B Cleavage of vcMMAE-Based Antibody-Drug Conjugate Is Not Drug Location or Monoclonal Antibody Carrier Specific. Bioconjug Chem. 2016 Apr 20;27(4):1040-9. doi: 10.1021/acs.bioconjchem.6b00055. PubMed PMID: 26914498.

6: Vaklavas C, Forero A. Management of metastatic breast cancer with second-generation antibody-drug conjugates: focus on glembatumumab vedotin (CDX-011, CR011-vcMMAE). BioDrugs. 2014 Jun;28(3):253-63. doi: 10.1007/s40259-014-0085-2. Review. PubMed PMID: 24496926.

7: 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. cAC10-vcMMAE, an anti-CD30-monomethyl auristatin E conjugate with potent and selective antitumor activity. Blood. 2003 Aug 15;102(4):1458-65. PubMed PMID: 12714494.

8: Klussman K, Mixan BJ, Cerveny CG, Meyer DL, Senter PD, Wahl AF. Secondary mAb--vcMMAE conjugates are highly sensitive reporters of antibody internalization via the lysosome pathway. Bioconjug Chem. 2004 Jul-Aug;15(4):765-73. PubMed PMID: 15264863.

9: Stagg NJ, Shen BQ, Brunstein F, Li C, Kamath AV, Zhong F, Schutten M, Fine BM. Peripheral neuropathy with microtubule inhibitor containing antibody drug conjugates: Challenges and perspectives in translatability from nonclinical toxicology studies to the clinic. Regul Toxicol Pharmacol. 2016 Dec;82:1-13. doi: 10.1016/j.yrtph.2016.10.012. PubMed PMID: 27773754.

10: Li H, Yu C, Jiang J, Huang C, Yao X, Xu Q, Yu F, Lou L, Fang J. An anti-HER2 antibody conjugated with monomethyl auristatin E is highly effective in HER2-positive human gastric cancer. Cancer Biol Ther. 2016 Apr 2;17(4):346-54. doi: 10.1080/15384047.2016.1139248. PubMed PMID: 26853765; PubMed Central PMCID: PMC4910924.

11: Dornan D, Bennett F, Chen Y, Dennis M, Eaton D, Elkins K, French D, Go MA, Jack A, Junutula JR, Koeppen H, Lau J, McBride J, Rawstron A, Shi X, Yu N, Yu SF, Yue P, Zheng B, Ebens A, Polson AG. Therapeutic potential of an anti-CD79b antibody-drug conjugate, anti-CD79b-vc-MMAE, for the treatment of non-Hodgkin lymphoma. Blood. 2009 Sep 24;114(13):2721-9. doi: 10.1182/blood-2009-02-205500. PubMed PMID: 19633198.

12: Li ZH, Zhang Q, Wang HB, Zhang YN, Ding D, Pan LQ, Miao D, Xu S, Zhang C, Luo PH, Naranmandura H, Chen SQ. Preclinical studies of targeted therapies for CD20-positive B lymphoid malignancies by Ofatumumab conjugated with auristatin. Invest New Drugs. 2014 Feb;32(1):75-86. doi: 10.1007/s10637-013-9995-y. PubMed PMID: 23903896.

13: Law CL, Cerveny CG, Gordon KA, Klussman K, Mixan BJ, Chace DF, Meyer DL, Doronina SO, Siegall CB, Francisco JA, Senter PD, Wahl AF. Efficient elimination of B-lineage lymphomas by anti-CD20-auristatin conjugates. Clin Cancer Res. 2004 Dec 1;10(23):7842-51. Erratum in: Clin Cancer Res. 2005 May 15;11(10):3969. PubMed PMID: 15585616.

14: Shinmi D, Nakano R, Mitamura K, Suzuki-Imaizumi M, Iwano J, Isoda Y, Enokizono J, Shiraishi Y, Arakawa E, Tomizuka K, Masuda K. Novel anticarcinoembryonic antigen antibody-drug conjugate has antitumor activity in the existence of soluble antigen. Cancer Med. 2017 Feb 17. doi: 10.1002/cam4.1003. [Epub ahead of print] PubMed PMID: 28211613.

15: Pan L, Zhao W, Lai J, Ding D, Zhang Q, Yang X, Huang M, Jin S, Xu Y, Zeng S, Chou JJ, Chen S. Sortase A-Generated Highly Potent Anti-CD20-MMAE Conjugates for Efficient Elimination of B-Lineage Lymphomas. Small. 2017 Feb;13(6). doi: 10.1002/smll.201602267. PubMed PMID: 27873460.

16: Tse KF, Jeffers M, Pollack VA, McCabe DA, Shadish ML, Khramtsov NV, Hackett CS, Shenoy SG, Kuang B, Boldog FL, MacDougall JR, Rastelli L, Herrmann J, Gallo M, Gazit-Bornstein G, Senter PD, Meyer DL, Lichenstein HS, LaRochelle WJ. CR011, a fully human monoclonal antibody-auristatin E conjugate, for the treatment of melanoma. Clin Cancer Res. 2006 Feb 15;12(4):1373-82. PubMed PMID: 16489096.

17: Vaklavas C, Forero-Torres A. Safety and efficacy of brentuximab vedotin in patients with Hodgkin lymphoma or systemic anaplastic large cell lymphoma. Ther Adv Hematol. 2012 Aug;3(4):209-25. doi: 10.1177/2040620712443076. PubMed PMID: 23606932; PubMed Central PMCID: PMC3627331.

18: Pan LY, Salas-Solano O, Valliere-Douglass JF. Conformation and dynamics of interchain cysteine-linked antibody-drug conjugates as revealed by hydrogen/deuterium exchange mass spectrometry. Anal Chem. 2014 Mar 4;86(5):2657-64. doi: 10.1021/ac404003q. PubMed PMID: 24512515.

19: Said N, Gahoual R, Kuhn L, Beck A, François YN, Leize-Wagner E. Structural characterization of antibody drug conjugate by a combination of intact, middle-up and bottom-up techniques using sheathless capillary electrophoresis - Tandem mass spectrometry as nanoESI infusion platform and separation method. Anal Chim Acta. 2016 Apr 28;918:50-9. doi: 10.1016/j.aca.2016.03.006. PubMed PMID: 27046210.

20: Zhou LT, Liu FY, Li Y, Peng YM, Liu YH, Li J. Gpnmb/osteoactivin, an attractive target in cancer immunotherapy. Neoplasma. 2012;59(1):1-5. doi: 10.4149/neo_2012_001. Review. PubMed PMID: 22017590.