MedKoo Biosciences, Inc.
Tel:   +1-919-636-5577    Fax:   +1-919-980-4831    Email:   sales@medkoo.com
Search
Login Register
Search
MedKoo Cat#: 206584 | Name: Mafodotin
Featured New

Description:

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

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

Mafodotin
Mafodotin
CAS#863971-19-1

Theoretical Analysis

MedKoo Cat#: 206584

Name: Mafodotin

CAS#: 863971-19-1

Chemical Formula: C49H76N6O11

Exact Mass: 924.5572

Molecular Weight: 925.18

Elemental Analysis: C, 63.61; H, 8.28; N, 9.08; O, 19.02

Price and Availability

Size Price Availability Quantity
10mg USD 250.00 2 Weeks
25mg USD 550.00 2 Weeks
50mg USD 950.00 2 Weeks
100mg USD 1,650.00 2 Weeks
200mg USD 2,950.00 2 Weeks
Bulk Inquiry
Buy Now
Add to Cart
Related CAS #
No Data
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/
Solvent mg/mL mM
Solubility
DMSO 100.0 108.09
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

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.
1: Sedlik C, Heitzmann A, Viel S, Ait Sarkouh R, Batisse C, Schmidt F, De La Rochere P, Amzallag N, Osinaga E, Oppezzo P, Pritsch O, Sastre-Garau X, Hubert P, Amigorena S, Piaggio E. Effective antitumor therapy based on a novel antibody-drug conjugate targeting the Tn carbohydrate antigen. Oncoimmunology. 2016 Apr 22;5(7):e1171434. doi: 10.1080/2162402X.2016.1171434. eCollection 2016 Jul. PubMed PMID: 27622021; PubMed Central PMCID: PMC5006918. 2: 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 Sep;174(6):911-22. doi: 10.1111/bjh.14145. Epub 2016 Jun 17. PubMed PMID: 27313079. 3: 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. 4: 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. 5: 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. 6: 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. 7: 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. 8: 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. 9: 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. 10: 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. 11: 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. 12: 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. 13: 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. 14: 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. 15: 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. 16: 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. 17: 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. 18: 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. 19: 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. 20: 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.