MAL-PEG4-MMAF

    WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 406806

CAS#: Unknown

Description: MAL-PEG4-MMAF is a maleimido functionalized derivative of MMAF (Monomethyl auristatin F) with PEG4 linker. MAL-PEG4-MMAF is a useful precursor for making antibody-drug conjugates (ADCs). The maleimido functional group can be easily conjugated to protein carriers (such as antibody or enzyme). Many antibody-drug conjugates (ADCs) currently in clinical trials employ maleimide-containing drug-linkers which are conjugated to antibody cysteine residues to form thiosuccinimide linkages.


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MAL-PEG4-MMAF is not in stock, but may be available through custom synthesis. For cost-effective reason, minimum 1 gram order is requested. The product will be characterized by NMR, HPLC and MS analysis. Purity (HPLC) is usually >98%. CoA, QC data, MSDS will be provided when product is successfully made. The estimated lead time is 2-3 months. Please send email to sales@medkoo.com to inquire quote.


Chemical Structure

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Theoretical Analysis

MedKoo Cat#: 406806
Name: MAL-PEG4-MMAF
CAS#: Unknown
Chemical Formula: C53H84N6O15
Exact Mass: 1044.5995
Molecular Weight: 1045.282
Elemental Analysis: C, 60.90; H, 8.10; N, 8.04; O, 22.96


Synonym: MAL-PEG4-MMAF

IUPAC/Chemical Name: ((2R,3R)-3-((2S)-1-((3R,5S)-4-((S)-2-((S)-17-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)-2-isopropyl-3-methyl-4-oxo-6,9,12,15-tetraoxa-3-azaheptadecanamido)-N,3-dimethylbutanamido)-3-methoxy-5-methylheptanoyl)pyrrolidin-2-yl)-3-methoxy-2-methylpropanoyl)-D-phenylalanine

InChi Key: JSTPVWCMSXHAEL-BZOJLTBTSA-N

InChi Code: InChI=1S/C53H84N6O15/c1-12-36(6)48(41(69-10)32-44(62)58-22-16-19-40(58)49(70-11)37(7)50(64)54-39(53(67)68)31-38-17-14-13-15-18-38)57(9)52(66)46(34(2)3)55-51(65)47(35(4)5)56(8)45(63)33-74-30-29-73-28-27-72-26-25-71-24-23-59-42(60)20-21-43(59)61/h13-15,17-18,20-21,34-37,39-41,46-49H,12,16,19,22-33H2,1-11H3,(H,54,64)(H,55,65)(H,67,68)/t36-,37+,39+,40-,41+,46-,47-,48?,49+/m0/s1

SMILES Code: CC(C)[C@H](N(C(COCCOCCOCCOCCN1C(C=CC1=O)=O)=O)C)C(N[C@H](C(N(C([C@@H](CC(N2CCC[C@H]2[C@H](OC)[C@H](C(N[C@@H](C(O)=O)CC3=CC=CC=C3)=O)C)=O)OC)[C@@H](C)CC)C)=O)C(C)C)=O


Technical Data

Appearance:
Solid powder

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

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: Lee L, Bounds D, Paterson J, Herledan G, Sully K, Seestaller-Wehr LM, Fieles WE, Tunstead J, McCahon L, Germaschewski FM, Mayes PA, Craigen JL, Rodriguez-Justo M, Yong KL. Evaluation of B cell maturation antigen as a target for antibody drug conjugate mediated cytotoxicity in multiple myeloma. Br J Haematol. 2016 Jun 17. doi: 10.1111/bjh.14145. [Epub ahead of print] PubMed PMID: 27313079.

2: Currier NV, Ackerman SE, Kintzing JR, Chen R, Filsinger Interrante M, Steiner A, Sato AK, Cochran JR. Targeted Drug Delivery with an Integrin-Binding Knottin-Fc-MMAF Conjugate Produced by Cell-Free Protein Synthesis. Mol Cancer Ther. 2016 Jun;15(6):1291-300. doi: 10.1158/1535-7163.MCT-15-0881. Epub 2016 Mar 29. PubMed PMID: 27197305.

3: Schumacher D, Hackenberger CP, Leonhardt H, Helma J. Current Status: Site-Specific Antibody Drug Conjugates. J Clin Immunol. 2016 May;36 Suppl 1:100-7. doi: 10.1007/s10875-016-0265-6. Epub 2016 Mar 22. PubMed PMID: 27003914; PubMed Central PMCID: PMC4891387.

4: Behrens CR, Ha EH, Chinn LL, Bowers S, Probst G, Fitch-Bruhns M, Monteon J, Valdiosera A, Bermudez A, Liao-Chan S, Wong T, Melnick J, Theunissen JW, Flory MR, Houser D, Venstrom K, Levashova Z, Sauer P, Migone TS, van der Horst EH, Halcomb RL, Jackson DY. Antibody-Drug Conjugates (ADCs) Derived from Interchain Cysteine Cross-Linking Demonstrate Improved Homogeneity and Other Pharmacological Properties over Conventional Heterogeneous ADCs. Mol Pharm. 2015 Nov 2;12(11):3986-98. doi: 10.1021/acs.molpharmaceut.5b00432. Epub 2015 Oct 2. PubMed PMID: 26393951.

5: Leal M, Wentland J, Han X, Zhang Y, Rago B, Duriga N, Spriggs F, Kadar E, Song W, McNally J, Shakey Q, Lorello L, Lucas J, Sapra P. Preclinical Development of an anti-5T4 Antibody-Drug Conjugate: Pharmacokinetics in Mice, Rats, and NHP and Tumor/Tissue Distribution in Mice. Bioconjug Chem. 2015 Nov 18;26(11):2223-32. doi: 10.1021/acs.bioconjchem.5b00205. Epub 2015 Jul 16. PubMed PMID: 26180901.

6: Scales SJ, Gupta N, Pacheco G, Firestein R, French DM, Koeppen H, Rangell L, Barry-Hamilton V, Luis E, Chuh J, Zhang Y, Ingle GS, Fourie-O'Donohue A, Kozak KR, Ross S, Dennis MS, Spencer SD. An antimesothelin-monomethyl auristatin e conjugate with potent antitumor activity in ovarian, pancreatic, and mesothelioma models. Mol Cancer Ther. 2014 Nov;13(11):2630-40. doi: 10.1158/1535-7163.MCT-14-0487-T. Epub 2014 Sep 23. PubMed PMID: 25249555.

7: Breij EC, de Goeij BE, Verploegen S, Schuurhuis DH, Amirkhosravi A, Francis J, Miller VB, Houtkamp M, Bleeker WK, Satijn D, Parren PW. An antibody-drug conjugate that targets tissue factor exhibits potent therapeutic activity against a broad range of solid tumors. Cancer Res. 2014 Feb 15;74(4):1214-26. doi: 10.1158/0008-5472.CAN-13-2440. Epub 2013 Dec 26. PubMed PMID: 24371232.

8: Simon M, Frey R, Zangemeister-Wittke U, Plückthun A. Orthogonal assembly of a designed ankyrin repeat protein-cytotoxin conjugate with a clickable serum albumin module for half-life extension. Bioconjug Chem. 2013 Nov 20;24(11):1955-66. doi: 10.1021/bc4004102. Epub 2013 Nov 11. PubMed PMID: 24168270.

9: Sapra P, Damelin M, Dijoseph J, Marquette K, Geles KG, Golas J, Dougher M, Narayanan B, Giannakou A, Khandke K, Dushin R, Ernstoff E, Lucas J, Leal M, Hu G, O'Donnell CJ, Tchistiakova L, Abraham RT, Gerber HP. Long-term tumor regression induced by an antibody-drug conjugate that targets 5T4, an oncofetal antigen expressed on tumor-initiating cells. Mol Cancer Ther. 2013 Jan;12(1):38-47. doi: 10.1158/1535-7163.MCT-12-0603. Epub 2012 Dec 5. PubMed PMID: 23223830.

10: Beck A, Lambert J, Sun M, Lin K. Fourth World Antibody-Drug Conjugate Summit: February 29-March 1, 2012, Frankfurt, Germany. MAbs. 2012 Nov-Dec;4(6):637-47. doi: 10.4161/mabs.21697. Epub 2012 Aug 22. PubMed PMID: 22909934; PubMed Central PMCID: PMC3502230.

11: Nilsson R, Mårtensson L, Eriksson SE, Sjögren HO, Tennvall J. Toxicity-reducing potential of extracorporeal affinity adsorption treatment in combination with the auristatin-conjugated monoclonal antibody BR96 in a syngeneic rat tumor model. Cancer. 2010 Feb 15;116(4 Suppl):1033-42. doi: 10.1002/cncr.24790. PubMed PMID: 20127954.

12: Jackson D, Gooya J, Mao S, Kinneer K, Xu L, Camara M, Fazenbaker C, Fleming R, Swamynathan S, Meyer D, Senter PD, Gao C, Wu H, Kinch M, Coats S, Kiener PA, Tice DA. A human antibody-drug conjugate targeting EphA2 inhibits tumor growth in vivo. Cancer Res. 2008 Nov 15;68(22):9367-74. doi: 10.1158/0008-5472.CAN-08-1933. PubMed PMID: 19010911.

13: Oflazoglu E, Stone IJ, Gordon K, Wood CG, Repasky EA, Grewal IS, Law CL, Gerber HP. Potent anticarcinoma activity of the humanized anti-CD70 antibody h1F6 conjugated to the tubulin inhibitor auristatin via an uncleavable linker. Clin Cancer Res. 2008 Oct 1;14(19):6171-80. doi: 10.1158/1078-0432.CCR-08-0916. Epub 2008 Sep 22. PubMed PMID: 18809969.

14: Doronina SO, Bovee TD, Meyer DW, Miyamoto JB, Anderson ME, Morris-Tilden CA, Senter PD. Novel peptide linkers for highly potent antibody-auristatin conjugate. Bioconjug Chem. 2008 Oct;19(10):1960-3. doi: 10.1021/bc800289a. Epub 2008 Sep 20. PubMed PMID: 18803412.

15: McDonagh CF, Kim KM, Turcott E, Brown LL, Westendorf L, Feist T, Sussman D, Stone I, Anderson M, Miyamoto J, Lyon R, Alley SC, Gerber HP, Carter PJ. Engineered anti-CD70 antibody-drug conjugate with increased therapeutic index. Mol Cancer Ther. 2008 Sep;7(9):2913-23. doi: 10.1158/1535-7163.MCT-08-0295. PubMed PMID: 18790772.

16: Stephan JP, Chan P, Lee C, Nelson C, Elliott JM, Bechtel C, Raab H, Xie D, Akutagawa J, Baudys J, Saad O, Prabhu S, Wong WL, Vandlen R, Jacobson F, Ebens A. Anti-CD22-MCC-DM1 and MC-MMAF conjugates: impact of assay format on pharmacokinetic parameters determination. Bioconjug Chem. 2008 Aug;19(8):1673-83. doi: 10.1021/bc800059t. Epub 2008 Jul 19. PubMed PMID: 18637680.

17: Smith LM, Nesterova A, Ryan MC, Duniho S, Jonas M, Anderson M, Zabinski RF, Sutherland MK, Gerber HP, Van Orden KL, Moore PA, Ruben SM, Carter PJ. CD133/prominin-1 is a potential therapeutic target for antibody-drug conjugates in hepatocellular and gastric cancers. Br J Cancer. 2008 Jul 8;99(1):100-9. doi: 10.1038/sj.bjc.6604437. Epub 2008 Jun 10. PubMed PMID: 18542072; PubMed Central PMCID: PMC2453027.

18: Temming K, Meyer DL, Zabinski R, Senter PD, Poelstra K, Molema G, Kok RJ. Improved efficacy of alphavbeta3-targeted albumin conjugates by conjugation of a novel auristatin derivative. Mol Pharm. 2007 Sep-Oct;4(5):686-94. Epub 2007 Aug 8. PubMed PMID: 17683157.

19: Jeffrey SC, Andreyka JB, Bernhardt SX, Kissler KM, Kline T, Lenox JS, Moser RF, Nguyen MT, Okeley NM, Stone IJ, Zhang X, Senter PD. Development and properties of beta-glucuronide linkers for monoclonal antibody-drug conjugates. Bioconjug Chem. 2006 May-Jun;17(3):831-40. PubMed PMID: 16704224.

20: Sutherland MS, Sanderson RJ, Gordon KA, Andreyka J, Cerveny CG, Yu C, Lewis TS, Meyer DL, Zabinski RF, Doronina SO, Senter PD, Law CL, Wahl AF. Lysosomal trafficking and cysteine protease metabolism confer target-specific cytotoxicity by peptide-linked anti-CD30-auristatin conjugates. J Biol Chem. 2006 Apr 14;281(15):10540-7. Epub 2006 Feb 16. PubMed PMID: 16484228.