| Size | Price | Stock | Qty |
|---|---|---|---|
| 10mg |
|
Purity: ≥98%
| ln Vitro |
MC-MMAF as part of ADCs: Anti-CD22-MC-MMAF and anti-CD79b-MC-MMAF showed potent in vivo efficacy in xenograft models (see In Vivo). In vitro, MC-MMAF is described as "more potent than MMAE" but is charged and relatively membrane-impermeable (reference 7 in paper). No specific in vitro IC50 values are given. [1]
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|---|---|
| ln Vivo |
MC-MMAF conjugated to anti-CD22 (non-binding to rat CD22) was tested in rat safety studies. At a single intravenous dose of 2,000 μg conjugated cytotoxic drug/m² (~20 mg ADC/kg), anti-CD22-MC-MMAF caused no body weight loss, no elevations in serum liver enzymes (ALT, AST), no hematologic toxicities (WBC, neutrophils, platelets), and no other significant adverse effects over 12 days, indicating reduced toxicity compared to cleavable linker ADCs (SPP-DM1 and MC-vc-PAB-MMAE). [1]
In efficacy studies, anti-CD22-MC-MMAF and anti-CD79b-MC-MMAF (administered at 405 μg conjugated drug/m² or 200 μg/m², respectively, ~7 mg ADC/kg and ~2.5 mg ADC/kg) induced tumor regression or elimination in Ramos xenograft models of non-Hodgkin's lymphoma. [1] |
| Animal Protocol |
For ADC efficacy studies (from [1]): Female CB17 ICR severe combined immunodeficiency mice (7-16 weeks) were implanted subcutaneously with tumor cells (e.g., Ramos, 5×10⁶ cells). When mean tumor size reached desired volume, mice (n=8-10 per group) were dosed intravenously via tail vein with ADCs. Anti-CD22-MC-MMAF was administered at 405 μg antibody-conjugated drug/m² (~7 mg ADC/kg) or anti-CD79b-MC-MMAF at 200 μg/m² (~2.5 mg ADC/kg). Tumor volumes measured over time. [1]
For rat safety studies: Female Sprague-Dawley rats (75-80 g, n=6/group) received a single intravenous dose of anti-CD22-MC-MMAF at 2,000 μg conjugated cytotoxic/m² (~20 mg ADC/kg). Body weights monitored daily; serum chemistry and hematology measured pre-dose, day 5, and day 12. Parameters included ALT, AST, ALP, WBC, neutrophils, platelets, etc. [1] For pharmacokinetic studies: Sprague-Dawley rats (225-250 g, n=4/group) received 10 mg/kg anti-CD22-MC-MMAF via jugular vein catheter. Blood samples collected at 0, 3 min, 1,6,24 h, and 2,3,4,7,10,15,21,28,35 days post-dose. Serum analyzed for total antibody and ADC concentration by ELISA. Pharmacokinetic variables calculated with WinNonlin. [1] |
| ADME/Pharmacokinetics |
For anti-CD22-MC-MMAF in rats (from [1]): Total antibody clearance = 29 mL/d/kg; ADC (drug-conjugated antibody) clearance = 11 mL/d/kg. The uncleavable linker ADC showed similar clearance kinetics for total antibody and drug-conjugated antibody, indicating minimal loss of drug from the antibody in circulation. In contrast, cleavable linker ADCs (SPP-DM1 and MC-vc-PAB-MMAE) exhibited faster drug loss and higher clearance of the ADC form. [1]
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| Toxicity/Toxicokinetics |
MC-MMAF as an uncleavable linker ADC (anti-CD22-MC-MMAF) showed no significant toxicity in rats at a dose of 2,000 μg conjugated cytotoxic/m² (~20 mg/kg). No body weight loss, no elevations in ALT/AST, no decreases in WBC, neutrophils, or platelets, and no changes in other clinical pathology variables compared to vehicle control. In contrast, cleavable linker ADCs (SPP-DM1 and MC-vc-PAB-MMAE) caused hepatic and hematologic toxicities. The improved tolerability of MC-MMAF ADCs is attributed to reduced systemic release of free drug and the charged nature of its metabolite (cysteine-MC-MMAF), which is less permeable to cells. [1]
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| References | |
| Additional Infomation |
MC-MMAF is an auristatin-based microtubule inhibitor (monomethylauristatin F) conjugated via an uncleavable maleimidocaproyl (MC) linker to antibodies. It is used in ADCs for cancer therapy, particularly for non-Hodgkin's lymphoma when targeted to CD22 or CD79b. The active metabolite is cysteine-MC-MMAF, which is released after lysosomal degradation of the ADC. Unlike cleavable linkers, uncleavable MC-MMAF ADCs require internalization and are less prone to off-target toxicity. [1]
|
| Molecular Formula |
C49H76N6O11
|
|---|---|
| Molecular Weight |
925.1614
|
| Exact Mass |
924.557
|
| CAS # |
863971-19-1
|
| Related CAS # |
McMMAF;863971-19-1
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| PubChem CID |
56949327
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| Appearance |
White to off-white solid powder
|
| Density |
1.2±0.1 g/cm3
|
| Boiling Point |
1052.0±65.0 °C at 760 mmHg
|
| Flash Point |
590.1±34.3 °C
|
| Vapour Pressure |
0.0±0.3 mmHg at 25°C
|
| Index of Refraction |
1.538
|
| LogP |
5.04
|
| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
11
|
| Rotatable Bond Count |
27
|
| Heavy Atom Count |
66
|
| Complexity |
1680
|
| Defined Atom Stereocenter Count |
9
|
| SMILES |
CC[C@H](C)[C@@H]([C@@H](CC(=O)N1CCC[C@H]1[C@@H]([C@@H](C)C(=O)N[C@@H](CC2=CC=CC=C2)C(=O)O)OC)OC)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](C(C)C)N(C)C(=O)CCCCCN3C(=O)C=CC3=O
|
| 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
|
| 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
|
| Synonyms |
SGD-1269; SGD 1269; SGD1269; mc-MMAF; mcMMAF; L4-MMAF; Maleimidocaproyl-MMAF; Maleimidocaproyl monomethylauristatin F; Mafodotin.
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ≥ 100 mg/mL (~108.09 mM)
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|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.0809 mL | 5.4045 mL | 10.8089 mL | |
| 5 mM | 0.2162 mL | 1.0809 mL | 2.1618 mL | |
| 10 mM | 0.1081 mL | 0.5404 mL | 1.0809 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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