PT2399 is a potent and orally available antagonist of HIF-2 with an IC50 of 6 nM, PT2399 selectively disrupts the heterodimerization of HIF-2α with HIF-1β. PT2399 dissociates HIF-2 (an obligatory heterodimer [HIF-2α/HIF-1β])14 in human Clear cell Renal Cell Carcinoma (ccRCC) suppressing tumorigenesis in 56% (10/18) lines. PT2399 (20 μM) causes off-target toxicity because it inhibits the proliferation of HIF-2α −/− 786-O cells and other cancer cell lines with undetectable HIF-2α. PT2399 (0.2-2 μM; 0-21 days) inhibits 786-O cells soft agar growth.
PT2399 reduces tumor cell density and increases fibrosis in RCC bearing mice. PT2399 (100 mg/kg; oral gavage; every 12 hours) is more active than SU 11248, and inhibits tumor growth in several SU 11248-resistant tumors in RCC bearing mice.
| Cell Experiment | |
|---|---|
| Cell lines | 786-O cells |
| Preparation method | PT2399 inhibited 786-O cell soft agar growth at 0.2-2 μM. |
| Concentrations | 0 μM, 0.2 μM, 2 μM |
| Incubation time | 0-21 days |
| Animal Experiment | |
|---|---|
| Animal models | Mice with RCC tumorgraft |
| Formulation | in 10% EtOH, 30% PEG400, 60% MCT |
| Dosages | 100 mg/kg |
| Administration | oral gavage every 12 hours |
| Molecular Weight | 419.32 |
| Formula | C17H10F5NO4S |
| CAS Number | 1672662-14-4 |
| Solubility (25°C) | DMSO 90 mg/mL |
| Storage | -20°C, sealed |
| Species | Mouse | Rat | Rabbit | Guinea pig | Hamster | Dog |
| Weight (kg) | 0.02 | 0.15 | 1.8 | 0.4 | 0.08 | 10 |
| Body Surface Area (m2) | 0.007 | 0.025 | 0.15 | 0.05 | 0.02 | 0.5 |
| Km factor | 3 | 6 | 12 | 8 | 5 | 20 |
| Animal A (mg/kg) = Animal B (mg/kg) multiplied by | Animal B Km |
| Animal A Km |
For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.
[3] Wenfang Chen, et al. Nature. Targeting renal cell carcinoma with a HIF-2 antagonist
| Related HIF Products |
|---|
| 3-Aminobenzoic acid
3-Aminobenzoic acid is a hypoxia-inducible factor-1α (HIF-1α) inhibitor. |
| Steppogenin
Steppogenin is a potent inhibitor of HIF-1α and DLL4, with IC50 values of 0.56 and 8.46 μM, respectively. |
| HIV-IN-7
Axl-IN-16 is a Axl inhibitor. |
| HIF-2α-IN-9
HIF-2α-IN-9 is an inhibitor ofHIF-2α. |
| PHD-IN-2
PHD-IN-2 is a PHD antagonist (IC50: < 5 nM). |
Products are for research use only. Not for human use. We do not sell to patients.
© Copyright 2010-2023 AbMole BioScience. All Rights Reserved.
