Mafodotin
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MedKoo CAT#: 206584

CAS#: 863971-19-1

Description: Mafodotin, also known as mc-MMAF and SGD-1269 or Maleimidocaproyl monomethylauristatin F, is a MMAF derivative having a Maleimidocaproyl linker (MC linker), which is ready to conjugate to antibody or other proteins or biopolymers. Mafodotin is a useful agent for make antibody drug conjugate (ADC) for targeted drug delivery. MMAF is a potent antimitotic and antitublin auristatin derivative with a charged C-terminal phenylalanine residue that attenuates its cytotoxic activity compared to its uncharged counterpart, MMAE.


Chemical Structure

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Mafodotin
CAS# 863971-19-1

Theoretical Analysis

MedKoo Cat#: 206584
Name: Mafodotin
CAS#: 863971-19-1
Chemical Formula: C49H76N6O11
Exact Mass: 924.56
Molecular Weight: 925.178
Elemental Analysis: C, 63.61; H, 8.28; N, 9.08; O, 19.02

Price and Availability

Size Price Availability Quantity
10mg USD 250 2 Weeks
25mg USD 550 2 Weeks
50mg USD 950 2 Weeks
100mg USD 1650 2 Weeks
200mg USD 2950 2 Weeks
Bulk inquiry

Synonym: SGD-1269; SGD 1269; SGD1269; mc-MMAF; mcMMAF; L4-MMAF; Maleimidocaproyl-MMAF; Maleimidocaproyl monomethylauristatin F; Mafodotin.

IUPAC/Chemical Name: ((2R,3R)-3-((S)-1-((3R,4S,5S)-4-((S)-2-((S)-2-(6-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)-N-methylhexanamido)-3-methylbutanamido)-N,3-dimethylbutanamido)-3-methoxy-5-methylheptanoyl)pyrrolidin-2-yl)-3-methoxy-2-methylpropanoyl)-L-phenylalanine

InChi Key: ORFNVPGICPYLJV-YTVPMEHESA-N

InChi Code: InChI=1S/C49H76N6O11/c1-12-32(6)44(37(65-10)29-41(59)54-27-19-22-36(54)45(66-11)33(7)46(60)50-35(49(63)64)28-34-20-15-13-16-21-34)53(9)48(62)42(30(2)3)51-47(61)43(31(4)5)52(8)38(56)23-17-14-18-26-55-39(57)24-25-40(55)58/h13,15-16,20-21,24-25,30-33,35-37,42-45H,12,14,17-19,22-23,26-29H2,1-11H3,(H,50,60)(H,51,61)(H,63,64)/t32-,33+,35-,36-,37+,42-,43-,44-,45+/m0/s1

SMILES Code: O=C(O)[C@H](CC1=CC=CC=C1)NC([C@H](C)[C@H]([C@H]2N(C(C[C@@H](OC)[C@@H](N(C)C([C@@H](NC([C@@H](N(C)C(CCCCCN3C(C=CC3=O)=O)=O)C(C)C)=O)C(C)C)=O)[C@@H](C)CC)=O)CCC2)OC)=O

Appearance: Light yellow waxy solid

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, not in water

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).

HS Tariff Code: 2934.99.9001

More Info: Monomethyl auristatin F (MMAF) is a synthetic antineoplastic agent. It is part of 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. 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. 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. (https://en.wikipedia.org/wiki/Monomethyl_auristatin_F)

Biological target: McMMAF is a protective group (maleimidocaproyl)-conjugated MMAF, which is a potent tubulin polymerization inhibitor. McMMAF can be used as a drug-linker for antibody-drug conjugates (ADC).
In vitro activity: All constructs had specific and high affinity binding to HER2, human and mouse albumins with values in the low- to sub-nM range. ZHER2-ABD-mcMMAF demonstrated the most potent cytotoxic effect on several HER2-over-expressing cell lines. Reference: Control Release. 2023 Feb 14;355:515-527. https://pubmed.ncbi.nlm.nih.gov/36773960/
In vivo activity: GSK2857916 treatment enhances intratumor immune cell infiltration and activation, delays tumor growth, and promotes durable complete regressions in immune-competent mice bearing EL4 lymphoma tumors expressing human BCMA (EL4-hBCMA). Responding mice are immune to rechallenge with EL4 parental and EL4-hBCMA cells, suggesting engagement of an adaptive immune response, immunologic memory, and tumor antigen spreading, which are abrogated upon depletion of endogenous CD8+ T cells. Reference: Mol Cancer Ther. 2021 Oct;20(10):1941-1955. https://pubmed.ncbi.nlm.nih.gov/34253590/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 100.0 108.09

Preparing Stock Solutions

The following data is based on the product molecular weight 925.18 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 1. Yin W, Xu T, Ding H, Zhang J, Bodenko V, Tretyakova MS, Belousov MV, Liu Y, Oroujeni M, Orlova A, Tolmachev V, Gräslund T, Vorobyeva A. Comparison of HER2-targeted affibody conjugates loaded with auristatin- and maytansine-derived drugs. J Control Release. 2023 Feb 14;355:515-527. doi: 10.1016/j.jconrel.2023.02.005. Epub ahead of print. PMID: 36773960. 2. von Achenbach C, Silginer M, Blot V, Weiss WA, Weller M. Depatuxizumab Mafodotin (ABT-414)-induced Glioblastoma Cell Death Requires EGFR Overexpression, but not EGFRY1068 Phosphorylation. Mol Cancer Ther. 2020 Jun;19(6):1328-1339. doi: 10.1158/1535-7163.MCT-19-0609. Epub 2020 May 5. PMID: 32371586. 3. Montes de Oca R, Alavi AS, Vitali N, Bhattacharya S, Blackwell C, Patel K, Seestaller-Wehr L, Kaczynski H, Shi H, Dobrzynski E, Obert L, Tsvetkov L, Cooper DC, Jackson H, Bojczuk P, Forveille S, Kepp O, Sauvat A, Kroemer G, Creighton-Gutteridge M, Yang J, Hopson C, Yanamandra N, Shelton C, Mayes P, Opalinska J, Barnette M, Srinivasan R, Smothers J, Hoos A. Belantamab Mafodotin (GSK2857916) Drives Immunogenic Cell Death and Immune-mediated Antitumor Responses In Vivo. Mol Cancer Ther. 2021 Oct;20(10):1941-1955. doi: 10.1158/1535-7163.MCT-21-0035. Epub 2021 Jul 12. PMID: 34253590; PMCID: PMC9398105. 4. Shi B, Wu M, Li Z, Xie Z, Wei X, Fan J, Xu Y, Ding D, Akash SH, Chen S, Cao S. Antitumor activity of a 5T4 targeting antibody drug conjugate with a novel payload derived from MMAF via C-Lock linker. Cancer Med. 2019 Apr;8(4):1793-1805. doi: 10.1002/cam4.2066. Epub 2019 Mar 7. PMID: 30843650; PMCID: PMC6488119.
In vitro protocol: 1. Yin W, Xu T, Ding H, Zhang J, Bodenko V, Tretyakova MS, Belousov MV, Liu Y, Oroujeni M, Orlova A, Tolmachev V, Gräslund T, Vorobyeva A. Comparison of HER2-targeted affibody conjugates loaded with auristatin- and maytansine-derived drugs. J Control Release. 2023 Feb 14;355:515-527. doi: 10.1016/j.jconrel.2023.02.005. Epub ahead of print. PMID: 36773960. 2. von Achenbach C, Silginer M, Blot V, Weiss WA, Weller M. Depatuxizumab Mafodotin (ABT-414)-induced Glioblastoma Cell Death Requires EGFR Overexpression, but not EGFRY1068 Phosphorylation. Mol Cancer Ther. 2020 Jun;19(6):1328-1339. doi: 10.1158/1535-7163.MCT-19-0609. Epub 2020 May 5. PMID: 32371586.
In vivo protocol: 1. Montes de Oca R, Alavi AS, Vitali N, Bhattacharya S, Blackwell C, Patel K, Seestaller-Wehr L, Kaczynski H, Shi H, Dobrzynski E, Obert L, Tsvetkov L, Cooper DC, Jackson H, Bojczuk P, Forveille S, Kepp O, Sauvat A, Kroemer G, Creighton-Gutteridge M, Yang J, Hopson C, Yanamandra N, Shelton C, Mayes P, Opalinska J, Barnette M, Srinivasan R, Smothers J, Hoos A. Belantamab Mafodotin (GSK2857916) Drives Immunogenic Cell Death and Immune-mediated Antitumor Responses In Vivo. Mol Cancer Ther. 2021 Oct;20(10):1941-1955. doi: 10.1158/1535-7163.MCT-21-0035. Epub 2021 Jul 12. PMID: 34253590; PMCID: PMC9398105. 2. Shi B, Wu M, Li Z, Xie Z, Wei X, Fan J, Xu Y, Ding D, Akash SH, Chen S, Cao S. Antitumor activity of a 5T4 targeting antibody drug conjugate with a novel payload derived from MMAF via C-Lock linker. Cancer Med. 2019 Apr;8(4):1793-1805. doi: 10.1002/cam4.2066. Epub 2019 Mar 7. PMID: 30843650; PMCID: PMC6488119.

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