Lys-SMCC-DM1 is the active metabolite of T-DM1. T-DM1 is an FDA approved HER2-targeting ADC (antibody-drug conjugate). Lys-SMCC-DM1 (also known as Lys-Nε-MCC-DM1) is a drug-linker conjugate in which DM1 acts as an inhibitor of tubulin polymerization. T-DM1 is a human epidermal growth factor receptor 2 (HER2)-targeting ADC for cancer treatment.
Physicochemical Properties
| Molecular Formula | C₅₃H₇₅CLN₆O₁₅S.CF3COOH |
| Molecular Weight | 1217.73 |
| Exact Mass | 1102.47 |
| CAS # | 1281816-04-3 |
| Related CAS # | (Rac)-Lys-SMCC-DM1 |
| PubChem CID | 71587969 |
| Appearance | White to off-white solid powder |
| LogP | 5.693 |
| Hydrogen Bond Donor Count | 5 |
| Hydrogen Bond Acceptor Count | 17 |
| Rotatable Bond Count | 19 |
| Heavy Atom Count | 76 |
| Complexity | 2200 |
| Defined Atom Stereocenter Count | 9 |
| SMILES | C[C@@H]1[C@@H]2C[C@]([C@@H](/C=C/C=C(/CC3=CC(=C(C(=C3)OC)Cl)N(C(=O)C[C@@H]([C@]4([C@H]1O4)C)OC(=O)[C@H](C)N(C)C(=O)CCSC5CC(=O)N(C5=O)CC6CCC(CC6)C(=O)NCCCC[C@@H](C(=O)O)N)C)\C)OC)(NC(=O)O2)O |
| InChi Key | UBRZDBDIKWWPEN-ANAFPORDSA-N |
| InChi Code | InChI=1S/C53H75ClN6O15S/c1-29-12-11-14-40(72-8)53(70)27-38(73-51(69)57-53)30(2)46-52(4,75-46)41(26-43(62)59(6)36-23-33(22-29)24-37(71-7)45(36)54)74-50(68)31(3)58(5)42(61)19-21-76-39-25-44(63)60(48(39)65)28-32-15-17-34(18-16-32)47(64)56-20-10-9-13-35(55)49(66)67/h11-12,14,23-24,30-32,34-35,38-41,46,70H,9-10,13,15-22,25-28,55H2,1-8H3,(H,56,64)(H,57,69)(H,66,67)/b14-11+,29-12+/t30-,31+,32?,34?,35+,38+,39+,40-,41+,46+,52+,53+/m1/s1 |
| Chemical Name | (2S)-2-amino-6-[[4-[[(3S)-3-[3-[[(2S)-1-[[(1S,2R,3S,5S,6S,16E,18E,20R,21S)-11-chloro-21-hydroxy-12,20-dimethoxy-2,5,9,16-tetramethyl-8,23-dioxo-4,24-dioxa-9,22-diazatetracyclo[19.3.1.110,14.03,5]hexacosa-10,12,14(26),16,18-pentaen-6-yl]oxy]-1-oxopropan-2-yl]-methylamino]-3-oxopropyl]sulfanyl-2,5-dioxopyrrolidin-1-yl]methyl]cyclohexanecarbonyl]amino]hexanoic acid |
| 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 (e.g. under nitrogen), 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) |
Biological Activity
| Targets | Maytansinoids |
| ln Vitro |
Lys-SMCC-DM1 have a minimal permeability level [1]. In KPL-4 and MDA-MB-468 cells, Lys-SMCC-DM1 exhibits cytotoxicity with IC50 values of 24.8 nM and 40.5 nM, respectively[2]. In MDCKII/SLC46A3 dC cells, Lys-SMCC-DM1 (200 μM) inhibits the uptake of estrone 3-sulfate by SLC46A3[2]. |
| References |
[1]. Bystander killing effect of DS-8201a, a novel anti-human epidermal growth factor receptor 2 antibody-drug conjugate, in tumors with human epidermal growth factor receptor 2 heterogeneity. Cancer Sci. 2016 Jul;107(7):1039-46. [2]. Identification of 5-Carboxyfluorescein as a Probe Substrate of SLC46A3 and Its Application in a Fluorescence-Based In Vitro Assay Evaluating the Interaction with SLC46A3. Mol Pharm. 2022 Dec 2. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~100 mg/mL (~90.60 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (2.27 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (2.27 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.5 mg/mL (2.27 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 4: 10% DMSO+ 40% PEG300+ 5% Tween-80+ 45% saline: ≥ 2.5 mg/mL (2.27 mM) (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.8212 mL | 4.1060 mL | 8.2120 mL | |
| 5 mM | 0.1642 mL | 0.8212 mL | 1.6424 mL | |
| 10 mM | 0.0821 mL | 0.4106 mL | 0.8212 mL |