CFT-8634 (CFT8634) is a BRD9-targeting PROTAC degrader with anticancer activity. Extracted from WO2021178920A1. May be used for synovial sarcoma and SMARCB1-deleted solid tumors
Physicochemical Properties
| Molecular Formula | C37H45F3N6O5 |
| Molecular Weight | 710.785619497299 |
| Exact Mass | 710.34 |
| CAS # | 2704617-96-7 |
| Related CAS # | (S,R)-CFT8634;2704617-95-6 |
| PubChem CID | 163203607 |
| Appearance | Light green to green solid powder |
| Density | 1.36±0.1 g/cm3(Predicted) |
| Boiling Point | 856.9±65.0 °C(Predicted) |
| LogP | 3.4 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 12 |
| Rotatable Bond Count | 9 |
| Heavy Atom Count | 51 |
| Complexity | 1360 |
| Defined Atom Stereocenter Count | 2 |
| SMILES | CC1=C(C(=O)N(C=C1C2=CC(=C(C(=C2)OC)CN3CC[C@@H](C(C3)(F)F)N4CCN(CC4)C5=C(C=C(C=C5)N[C@H]6CCC(=O)NC6=O)F)OC)C)C |
| InChi Key | GNRGNRCQXHMQQV-ZQAZVOLISA-N |
| InChi Code | InChI=1S/C37H45F3N6O5/c1-22-23(2)36(49)43(3)19-26(22)24-16-31(50-4)27(32(17-24)51-5)20-44-11-10-33(37(39,40)21-44)46-14-12-45(13-15-46)30-8-6-25(18-28(30)38)41-29-7-9-34(47)42-35(29)48/h6,8,16-19,29,33,41H,7,9-15,20-21H2,1-5H3,(H,42,47,48)/t29-,33-/m0/s1 |
| Chemical Name | (3S)-3-[4-[4-[(4S)-1-[[2,6-dimethoxy-4-(1,4,5-trimethyl-6-oxopyridin-3-yl)phenyl]methyl]-3,3-difluoropiperidin-4-yl]piperazin-1-yl]-3-fluoroanilino]piperidine-2,6-dione |
| 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: (1). This product requires protection from light (avoid light exposure) during transportation and storage.(2). 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
| References |
[1]. Compounds for targeted degradation of brd9. WO2021178920A1. [2]. Brian A, et.al. A Phase 1/2 Study of CFT8634, a Novel Bifunctional Degradation Activating Compound (BIDACmDegrader Of BRD9, in Synovial Sarcoma and SMARCB1-null Tumors. |
| Additional Infomation | Sendegobresib is an orally bioavailable heterobifunctional protein degrader of bromodomain-containing protein 9 (BRD9; sarcoma antigen NY-SAR-29; rhabdomyosarcoma antigen MU-RMS-40.8), with potential antineoplastic activity. Sendegobresib is comprised of an E3 ligase-binding moiety and a BRD9-binding moiety. Upon oral administration, sendegobresib targets and binds to BRD9 with its BRD9-binding moiety. Upon BRD9 binding, the E3 ligase-binding moiety binds to cereblon (CRBN), a component of the CRL4-CRBN E3 ubiquitin ligase complex, which directs proteins for destruction, resulting in the proteasome-mediated degradation of BRD9. This leads to an inhibition of the growth of tumor cells that rely on BRD9 for survival. BRD9, a component of one form of the Brg/Brahma-Associated Factor (BAF) complex, is needed for the survival of certain cancer cells due to mutations. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~100 mg/mL (~140.69 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (3.52 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 (3.52 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 (3.52 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.4069 mL | 7.0344 mL | 14.0689 mL | |
| 5 mM | 0.2814 mL | 1.4069 mL | 2.8138 mL | |
| 10 mM | 0.1407 mL | 0.7034 mL | 1.4069 mL |