Physicochemical Properties
| Molecular Formula | C24H22N6O4 |
| Molecular Weight | 458.469284534454 |
| Exact Mass | 458.17 |
| Elemental Analysis | C, 62.87; H, 4.84; N, 18.33; O, 13.96 |
| CAS # | 2320462-65-3 |
| Related CAS # | 2320462-65-3; |
| PubChem CID | 142587219 |
| Appearance | White to off-white solid powder |
| LogP | 2.7 |
| Hydrogen Bond Donor Count | 3 |
| Hydrogen Bond Acceptor Count | 10 |
| Rotatable Bond Count | 7 |
| Heavy Atom Count | 34 |
| Complexity | 705 |
| Defined Atom Stereocenter Count | 1 |
| SMILES | CC1(C2=C(C=CC(=C2)NC3=NC=C(C(=N3)N[C@H](CO)C4=CC=CC=C4)C5=NN=CO5)C(=O)O1)C |
| InChi Key | RVSSNRBUPQUIEG-LJQANCHMSA-N |
| InChi Code | InChI=1S/C24H22N6O4/c1-24(2)18-10-15(8-9-16(18)22(32)34-24)27-23-25-11-17(21-30-26-13-33-21)20(29-23)28-19(12-31)14-6-4-3-5-7-14/h3-11,13,19,31H,12H2,1-2H3,(H2,25,27,28,29)/t19-/m1/s1 |
| Chemical Name | 5-[[4-[[(1S)-2-hydroxy-1-phenylethyl]amino]-5-(1,3,4-oxadiazol-2-yl)pyrimidin-2-yl]amino]-3,3-dimethyl-2-benzofuran-1-one |
| Synonyms | HPK1-IN-7 ; HPK1-IN 7, HPK1-IN7 |
| 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 | HPK1 (IC50 = 2.6 nM); GLK/MAP4K3 (IC50 = 140 nM); IRAK4 (IC50 = 59 nM); Fms/CSFR (IC50 = 3.2 nM ); FLT3 (IC50 = 25.4 nM);AMPKA1 (IC50 = 44.3 nM); cKIT (IC50 = 45.7 nM); MST1(IC50 = 55.1 nM) |
| ln Vivo |
In a syngeneic tumor model of colorectal cancer, HPK1-IN-7 (100 mg/kg; p.o.; twice daily for 28 days) exhibits a significant enhancement of anti-PD1 efficacy. HPK1-IN-7 (compound 24) has a volume of distribution of 4.4 L/kg and a moderate plasma clearance of 43 mL/min/kg. It is administered intravenously to mice at a dose of 1 mg/kg. The AUC0-24h was 19 M•h and the Cmax was 5.3 M following oral administration (20 mg/kg). Based on these pharmacokinetics studies, the calculated oral bioavailability is approximately 100%. |
| Animal Protocol |
Animal Model:Mice (MC38 syngeneic tumor model) Dosage: 100mg/kg Administration: Oral; twice daily for 28 days Result: increased the anti-PD1 treatment's effectiveness, achieving a 100% cure rate as opposed to a 20% cure rate with anti-PD1 alone. |
| References |
Discovery of Orally Active Isofuranones as Potent, Selective Inhibitors of Hematopoetic Progenitor Kinase 1. |
Solubility Data
| Solubility (In Vitro) | DMSO: ~125.0 mg/mL (~272.7 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.54 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 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 20.8 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1812 mL | 10.9058 mL | 21.8117 mL | |
| 5 mM | 0.4362 mL | 2.1812 mL | 4.3623 mL | |
| 10 mM | 0.2181 mL | 1.0906 mL | 2.1812 mL |