Monomethyl auristatin F

Monomethyl auristatin F (MMAF) is a synthetic antineoplastic agent.[1] It is part of the approved drug belantamab mafodotin in multiple myeloma and some experimental anti-cancer antibody-drug conjugates such as vorsetuzumab mafodotin and SGN-CD19A. In International Nonproprietary Names for MMAF-antibody-conjugates, the name mafodotin refers to MMAF plus its attachment structure to the antibody.[2]

Monomethyl auristatin F

Names
IUPAC name (S)-2-((2R,3R)-3-((S)-1-((3R,4S,5S)-4-((S)-N,3-dimethyl-2-((S)-3-methyl-2-(methylamino)butanamido)butanamido)-3-methoxy-5-methylheptanoyl)pyrrolidin-2-yl)-3-methoxy-2-methylpropanamido)-3-phenylpropanoic acid
Identifiers
CAS Number	745017-94-1
3D model (JSmol)	Interactive image
Abbreviations	MMAF
ChemSpider	8570614
PubChem CID	10395173
UNII	1Z1AI9IW5L
InChI InChI=1S/C39H65N5O8/c1-12-25(6)34(43(9)38(48)33(24(4)5)42-37(47)32(40-8)23(2)3)30(51-10)22-31(45)44-20-16-19-29(44)35(52-11)26(7)36(46)41-28(39(49)50)21-27-17-14-13-15-18-27/h13-15,17-18,23-26,28-30,32-35,40H,12,16,19-22H2,1-11H3,(H,41,46)(H,42,47)(H,49,50)/t25-,26+,28-,29-,30+,32-,33-,34-,35+/m0/s1 Key: MFRNYXJJRJQHNW-DEMKXPNLSA-N InChI=1/C39H65N5O8/c1-12-25(6)34(43(9)38(48)33(24(4)5)42-37(47)32(40-8)23(2)3)30(51-10)22-31(45)44-20-16-19-29(44)35(52-11)26(7)36(46)41-28(39(49)50)21-27-17-14-13-15-18-27/h13-15,17-18,23-26,28-30,32-35,40H,12,16,19-22H2,1-11H3,(H,41,46)(H,42,47)(H,49,50)/t25-,26+,28-,29-,30+,32-,33-,34-,35+/m0/s1 Key: MFRNYXJJRJQHNW-DEMKXPNLBL
SMILES O=C(N2[C@H]([C@H](OC)[C@H](C(=O)N[C@H](C(=O)O)Cc1ccccc1)C)CCC2)C[C@@H](OC)[C@@H](N(C(=O)[C@@H](NC(=O)[C@@H](NC)C(C)C)C(C)C)C)[C@@H](C)CC
Properties
Chemical formula	C39H65N5O8
Molar mass	731.976 g·mol^−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Infobox references

Mechanism of action

Monomethyl auristatin F is an antimitotic agent which inhibits cell division by blocking the polymerisation of tubulin. It is linked to an antibody with high affinity to structures on cancer cells, causing MMAF to accumulate in such cells.[3]

Chemistry

MMAF is actually desmethyl-auristatin F; that is, the N-terminal amino group has only one methyl substituent instead of two as in auristatin F itself.[3]

Structure of conjugate of MMAF with a monoclonal antibody (MAB). The attachment group consists of maleimide and caproic acid. About eight such structures are bound to a single antibody molecule.[3]

See also

• Monomethyl auristatin E

References

1. Tai, Y. T.; Mayes, P. A.; Acharya, C; Zhong, M. Y.; Cea, M; Cagnetta, A; Craigen, J; Yates, J; Gliddon, L; Fieles, W; Hoang, B; Tunstead, J; Christie, A. L.; Kung, A. L.; Richardson, P; Munshi, N. C.; Anderson, K. C. (2014). "Novel afucosylated anti-B cell maturation antigen-monomethyl auristatin F antibody-drug conjugate (GSK2857916) induces potent and selective anti-multiple myeloma activity". Blood. 123 (20): 3128–38. doi:10.1182/blood-2013-10-535088. PMC 4023420. PMID 24569262.
2. Statement on a nonproprietary name adopted by the USAN Council: Mafodotin
3. Dosio, F.; Brusa, P.; Cattel, L. (2011). "Immunotoxins and Anticancer Drug Conjugate Assemblies: The Role of the Linkage between Components". Toxins. 3 (12): 848–883. doi:10.3390/toxins3070848. PMC 3202854. PMID 22069744.