Physicochemical Properties
| Molecular Formula | C22H14F7N5O |
| Molecular Weight | 497.37 |
| Exact Mass | 497.11 |
| Elemental Analysis | C, 53.13; H, 2.84; F, 26.74; N, 14.08; O, 3.22 |
| CAS # | 2832047-80-8 |
| PubChem CID | 165413021 |
| Appearance | White to off-white solid powder |
| LogP | 3.2 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 12 |
| Rotatable Bond Count | 5 |
| Heavy Atom Count | 35 |
| Complexity | 785 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | C1(CC(N(CC#CC2=NN=C(N)C=C2)C2=CC=C(F)C=C2)=O)=NC=C(C(F)(F)F)C=C1C(F)(F)F |
| InChi Key | LHFFKHVGAKIDNO-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C22H14F7N5O/c23-14-3-6-16(7-4-14)34(9-1-2-15-5-8-19(30)33-32-15)20(35)11-18-17(22(27,28)29)10-13(12-31-18)21(24,25)26/h3-8,10,12H,9,11H2,(H2,30,33) |
| Chemical Name | N-[3-(6-aminopyridazin-3-yl)prop-2-ynyl]-2-[3,5-bis(trifluoromethyl)pyridin-2-yl]-N-(4-fluorophenyl)acetamide |
| Synonyms | RP6685; RP-6685; RP 6685 |
| 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 |
| 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 | Polθ ( IC50 = 5.8 nM ) |
| ln Vitro | RP-6685 is inert against ATPase activity and has an IC50 of 550 pM for pol activity against full-length Polθ [1]. With an IC50 of 0.94 μM, RP-6685 inhibits Polθ in HEK293 LIG4-/-cells[1]. |
| ln Vivo | In BRCA2-deficient HCT116 mice, RP-6685 (80 mg/kg; oral; BID for 21 days) showed strong anti-tumor effectiveness [1]. |
| Animal Protocol |
Animal/Disease Models: Female CD1 nude mice (HCT116 BRCA2+/+ and BRCA2-/- xenograft tumor models)[1] Doses: 80 mg/kg Route of Administration: po ; BID for 21 days Experimental Results: demonstrated tumor regression during the first 8 days of treatment in BRCA2-/- HCT116 model, while did not inhibit tumor growth in BRCA2+/+ HCT116 tumors mice. Animal/Disease Models: CD1 mice (20-30 g) [1] Doses: 2.5 mg/kg Route of Administration: iv or po; single dosage Experimental Results: CL (mL/min/kg) Vdss (L/kg) t1/2 (h) F (%) 36.8 1.1 0.4 66 |
| References |
[1]. Identification of RP-6685, an Orally Bioavailable Compound that Inhibits the DNA Polymerase Activity of Polθ. J Med Chem. 2022 Sep 20. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~100 mg/mL (~201.1 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.18 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 20.8 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 | 2.0106 mL | 10.0529 mL | 20.1058 mL | |
| 5 mM | 0.4021 mL | 2.0106 mL | 4.0212 mL | |
| 10 mM | 0.2011 mL | 1.0053 mL | 2.0106 mL |