| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 50mg |
|
||
| Other Sizes |
| Targets |
Microtubules/Tubulin. After the OtBu group is removed and the MMAF is conjugated to an antibody via a linker, the released MMAF payload potently inhibits tubulin polymerization, leading to G2/M cell cycle arrest and apoptosis in targeted cancer cells.
|
|---|---|
| ln Vitro |
In cell‑free assays, MMAF‑OtBu itself is inactive due to the protected C‑terminus. However, after deprotection to yield free MMAF, the compound is a highly potent tubulin polymerization inhibitor. It inhibits the proliferation of various cancer cell lines with IC50 values in the low nanomolar range. The OtBu group does not contribute to this activity.
|
| Enzyme Assay |
A general cell‑free protocol for assessing tubulin polymerization inhibition: Purified tubulin is incubated in a polymerization buffer with GTP. The process of tubulin polymerization is monitored by the increase in light scattering (absorbance at 340 nm) at 37degC. The addition of active MMAF (after OtBu removal) will inhibit this polymerization, leading to a reduced absorbance signal, from which an IC50 can be calculated.
|
| Cell Assay |
A general cellular protocol for a MMAF-based ADC: Cancer cells expressing the target antigen are seeded in 96‑well plates. The MMAF-based ADC (synthesized from MMAF-OtBu) is added at serial dilutions (0.001‑10 ug/mL). After 96 hours, cell viability is assessed by the CellTiter‑Glo or MTT assay. A reduction in cell viability indicates that the ADC was internalized, processed, and the active MMAF was released.
|
| Animal Protocol |
A general animal protocol for a MMAF-based ADC: Nude mice bearing subcutaneous xenografts of target‑positive human tumors are randomized into groups. The MMAF-based ADC is administered intravenously at doses of 1, 3, and 10 mg/kg once weekly for three weeks. Tumor volume is measured twice weekly. A significant tumor growth inhibition or regression compared to the vehicle control indicates efficacy.
|
| ADME/Pharmacokinetics |
General PK protocol for a MMAF-based ADC: The ADC is administered intravenously to cynomolgus monkeys. Blood samples are collected over 21 days. Serum concentrations of total antibody are measured by ELISA, and conjugated antibody concentrations are measured by a similar assay using an anti-MMAF antibody. The free MMAF payload in plasma is measured by LC‑MS/MS to assess linker stability.
|
| Toxicity/Toxicokinetics |
General toxicity protocol for a MMAF-based ADC: A 28‑day repeat‑dose intravenous toxicity study is performed in cynomolgus monkeys. The ADC is administered at doses of 5, 15, and 45 mg/kg once weekly. Parameters include clinical signs, body weight, hematology (with special attention to neutrophil count), serum chemistry, and histopathology of the bone marrow and gastrointestinal tract. Peripheral neuropathy is a potential toxicity of auristatin ADCs.
|
| References | |
| Additional Infomation |
MMAF‑OtBu has the molecular formula C43H₇3N₅O₈ and a molecular weight of 788.07 g/mol. It is a modified MMAF used as an ADC cytotoxin. The OtBu protecting group is essential for chemical synthesis, allowing for the introduction of a linker at the C‑terminus without side reactions. The compound is soluble in DMSO and is stored at -20degC, sealed and away from moisture. It is a research chemical for ADC development.
|
| Molecular Formula |
C43H73N5O8
|
|---|---|
| Molecular Weight |
788.07
|
| Exact Mass |
787.546
|
| CAS # |
745017-95-2
|
| PubChem CID |
57587862
|
| Appearance |
Solid powder
|
| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
9
|
| Rotatable Bond Count |
23
|
| Heavy Atom Count |
56
|
| Complexity |
1270
|
| 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)OC(C)(C)C)OC)OC)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](C(C)C)NC
|
| InChi Key |
HMBFRLXQUOOKLK-VFSYNPLYSA-N
|
| InChi Code |
InChI=1S/C43H73N5O8/c1-15-28(6)37(47(12)41(52)36(27(4)5)46-40(51)35(44-11)26(2)3)33(54-13)25-34(49)48-23-19-22-32(48)38(55-14)29(7)39(50)45-31(42(53)56-43(8,9)10)24-30-20-17-16-18-21-30/h16-18,20-21,26-29,31-33,35-38,44H,15,19,22-25H2,1-14H3,(H,45,50)(H,46,51)/t28-,29+,31-,32-,33+,35-,36-,37-,38+/m0/s1
|
| Chemical Name |
tert-butyl (2S)-2-[[(2R,3R)-3-methoxy-3-[(2S)-1-[(3R,4S,5S)-3-methoxy-5-methyl-4-[methyl-[(2S)-3-methyl-2-[[(2S)-3-methyl-2-(methylamino)butanoyl]amino]butanoyl]amino]heptanoyl]pyrrolidin-2-yl]-2-methylpropanoyl]amino]-3-phenylpropanoate
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
DMSO : 50 mg/mL (63.45 mM; with sonication (<60°C))
|
|---|---|
| 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 | 1.2689 mL | 6.3446 mL | 12.6892 mL | |
| 5 mM | 0.2538 mL | 1.2689 mL | 2.5378 mL | |
| 10 mM | 0.1269 mL | 0.6345 mL | 1.2689 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
