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| 25mg |
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Purity: ≥98%
VcMMAE (mc-vc-PAB-MMAE), a derivative of MMAE (monomethyl auristatin E) with a valine-citrulline (Vc) linker, is a drug-linker conjugate for ADC (antibody-drug-conjugate) with potent antitumor activity by utilizing the anti-mitotic agent, monomethyl auristatin E (MMAE), linked via the lysosomally cleavable dipeptide, valine-citrulline (vc). VcMMAE is a anti-mitotic agent, monomethyl auristatin E (MMAE), linked via the lysosomally cleavable dipeptide, valine-citrulline (vc). Monomethyl auristatin E (MMAE) is a synthetic antineoplastic agent. Because of its toxicity, it cannot be used as a drug itself; instead, it is linked to a monoclonal antibody (MAB) which directs it to the cancer cells. In International Nonproprietary Names for MMAE-MAB-conjugates, the name vedotin refers to MMAE plus its linking structure to the antibody. It is a potent antimitotic drug derived from peptides occurring in marine shell-less mollusc Dolabella auricularia called dolastatins which show potent activity in preclinical studies, both in vitro and in vivo, against a range of lymphomas, leukemia and solid tumors. These drugs show potency of up to 200 times that of vinblastine, another antimitotic drug used for Hodgkin lymphoma as well as other types of cancer
| Targets |
Auristatin
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|---|---|
| ln Vitro |
Because of its membrane permeability, monomethyl auristatin E (MMAE) can effectively be released from SGN-35 within CD30+ cancer cells and cause cytotoxicity in bystander cells[1]. Colorectal and pancreatic cancer cells were sensitized to IR by MMAE in a schedule- and dose-dependent way that was correlated with mitotic arrest. Reduced clonogenic survival and more DNA double strand breaks in exposed cells are signs of radiosensitization[2].
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| ln Vivo |
Tumor-targeted ACPP-cRGD-MMAE combined with IR results in a more robust and noticeably prolonged tumor regression in xenograft models. In contrast, monomethyl auristatin E (MMAE) plus IR causes a delay in tumor growth[2].
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| Enzyme Assay |
MMAE is efficiently released from SGN-35 within CD30(+) cancer cells and, due to its membrane permeability, is able to exert cytotoxic activity on bystander cells. This provides mechanistic insight into the pronounced preclinical and clinical antitumor activities observed with SGN-35 [1].
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| Cell Assay |
Cells treated with ionizing radiation (IR) and monomethyl auristatin E (MMAE, 5 nM) are collected and lysed in RIPA buffer containing inhibitors of phosphatase and protease. 30μg of the lysate are electrophoresed on 4-12% Bis-Tris gels, then they are moved to PVDF membranes and the relevant primary antibodies are added. ECL is used to develop blots.
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| Animal Protocol |
Female athymic nu/nu mice aged 6-8 weeks are given a 1:1 Matrigel and PBS solution subcutaneously injected into their thighs, containing 5×106 HCT-116 or PANC-1 cells. After administering ACPP-cRGD-MMAE intravenously (IV) or orally (IR) (6 nmoles/day, totaling 18 nmoles), the mice are given the treatment. Tumor tissue is then removed, paraffin embedded, formalin fixed, and stained with the appropriate antibodies. Using the UltraMap system, DAB is used as a chromagen and the primary antibody is used at a 1:250 dilution for visualization.
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| References |
| Molecular Formula |
C68H105N11O15
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|---|---|
| Molecular Weight |
1316.6260
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| Exact Mass |
1315.779
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| Elemental Analysis |
C, 62.03; H, 8.04; N, 11.70; O, 18.23
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| CAS # |
646502-53-6
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| Related CAS # |
VcMMAE;646502-53-6
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| PubChem CID |
46944733
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| Appearance |
White to off-white solid powder
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| Density |
1.2±0.1 g/cm3
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| Boiling Point |
1347.6±65.0 °C at 760 mmHg
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| Flash Point |
768.8±34.3 °C
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| Vapour Pressure |
0.0±0.3 mmHg at 25°C
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| Index of Refraction |
1.556
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| LogP |
6.04
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| Hydrogen Bond Donor Count |
8
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| Hydrogen Bond Acceptor Count |
15
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| Rotatable Bond Count |
39
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| Heavy Atom Count |
94
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| Complexity |
2520
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| Defined Atom Stereocenter Count |
12
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| SMILES |
O(C([H])([H])[H])[C@]([H])([C@]([H])(C(N([H])[C@]([H])(C([H])([H])[H])[C@]([H])(C1C([H])=C([H])C([H])=C([H])C=1[H])O[H])=O)C([H])([H])[H])[C@]1([H])C([H])([H])C([H])([H])C([H])([H])N1C(C([H])([H])[C@]([H])([C@]([H])([C@@]([H])(C([H])([H])[H])C([H])([H])C([H])([H])[H])N(C([H])([H])[H])C([C@]([H])(C([H])(C([H])([H])[H])C([H])([H])[H])N([H])C([C@]([H])(C([H])(C([H])([H])[H])C([H])([H])[H])N(C(=O)OC([H])([H])C1C([H])=C([H])C(=C([H])C=1[H])N([H])C([C@]([H])(C([H])([H])C([H])([H])C([H])([H])N([H])C(N([H])[H])=O)N([H])C([C@]([H])(C([H])(C([H])([H])[H])C([H])([H])[H])N([H])C(C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])N1C(C([H])=C([H])C1=O)=O)=O)=O)=O)C([H])([H])[H])=O)=O)OC([H])([H])[H])=O
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| InChi Key |
NLMBVBUNULOTNS-HOKPPMCLSA-N
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| InChi Code |
InChI=1S/C68H105N11O15/c1-15-43(8)59(51(92-13)38-55(83)78-37-23-27-50(78)61(93-14)44(9)62(85)71-45(10)60(84)47-24-18-16-19-25-47)76(11)66(89)57(41(4)5)75-65(88)58(42(6)7)77(12)68(91)94-39-46-29-31-48(32-30-46)72-63(86)49(26-22-35-70-67(69)90)73-64(87)56(40(2)3)74-52(80)28-20-17-21-36-79-53(81)33-34-54(79)82/h16,18-19,24-25,29-34,40-45,49-51,56-61,84H,15,17,20-23,26-28,35-39H2,1-14H3,(H,71,85)(H,72,86)(H,73,87)(H,74,80)(H,75,88)(H3,69,70,90)/t43-,44+,45+,49-,50-,51+,56-,57-,58-,59-,60+,61+/m0/s1
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| Chemical Name |
4-((S)-2-((S)-2-(6-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)hexanamido)-3-methylbutanamido)-5-ureidopentanamido)benzyl ((S)-1-(((S)-1-(((3R,4S,5S)-1-((S)-2-((1R,2R)-3-(((1S,2R)-1-hydroxy-1-phenylpropan-2-yl)amino)-1-methoxy-2-methyl-3-oxopropyl)pyrrolidin-1-yl)-3-methoxy-5-methyl-1-oxoheptan-4-yl)(methyl)amino)-3-methyl-1-oxobutan-2-yl)amino)-3-methyl-1-oxobutan-2-yl)(methyl)carbamate
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| Synonyms |
mc-vc-PAB-MMAE; VcMMAE; Vc-MMAE; MC-VC-PAB-MMAE; MMAE Vc linker, MMAE antibody conjugate
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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 Note: 1) This product is not stable in solution, please use freshly prepared working solution for optimal results; 2) Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| 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 : ≥ 54 mg/mL (~41.0 mM)
H2O : < 0.1 mg/mL Ethanol: ~50 mg/mL (38 mM) |
|---|---|
| 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 | 0.7595 mL | 3.7976 mL | 7.5951 mL | |
| 5 mM | 0.1519 mL | 0.7595 mL | 1.5190 mL | |
| 10 mM | 0.0760 mL | 0.3798 mL | 0.7595 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.
 MMAE has increased potency compared to paclitaxel in tumor cells.Cancer Res.2015 Apr 1;75(7):1376-1387. |
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 MMAE increases IR induced DNA double strand breaks in a schedule and dose dependent manner.Cancer Res.2015 Apr 1;75(7):1376-1387. |
 MMAE decreases clonogenic survival of irradiated tumor cells.Cancer Res.2015 Apr 1;75(7):1376-1387. |
 MMAE increases DNA damage response in irradiated tumor cells.Cancer Res.2015 Apr 1;75(7):1376-1387. |
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 ACPP-cRGD-MMAE in combination with IR significantly reduces tumor growth.Cancer Res.2015 Apr 1;75(7):1376-1387. |
 Activatable cell penetrating peptides are cleaved in irradiated tumor microenvironments.Cancer Res.2015 Apr 1;75(7):1376-1387. |
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