RTx-303
RTx-303 is an orally active, selective DNA polymerase θ (Polθ) inhibitor (IC50 = 5.1 nM). RTx-303 exhibits significantly high cellular potency and strongly potentiates PARPi in BRCA1/2 mutant cells and patient-derived xenograft models. RTx-303 can be used for the study of BRCA2-mutated breast cancer.
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- No. CAS: 3035072-99-9
- Fòrmula: C24H22D3F7N4O4
- Peso molecular:569.49
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Almacenamiento:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Actividad biológica
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DNA Polymerase |
RTx-303 significantly inhibits Polθ-pol activity, but has no significant effect on other DNA polymerases (such as Polβ, Polη, Polγ, etc)[1].
RTx-303 (10 μM) shows no significant inhibition of most kinases (% activity >90%), and only mild inhibition of a few kinases, such as PASK (75% activity) and ATR/ATRIP (77% activity)[1].
RTx-303 shows an IC50 of 81.2 nM against HRD cells (HCT116 BRCA2-/-) and >1280 nM against HR-proficient cells (HCT116 BRCA2+/+), demonstrating >100-fold selectivity[1].
RTx-303 (5 μM, 5 days) in combination with Olaparib (HY-10162) significantly reduces the IC50 of ID8 BRCA2-/- cells (from 2 μM to 0.12 μM) and restores Olaparib sensitivity in PARPi-resistant cells[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
| Species | Dose | Route | T1/2 | Cmax | AUClast | Tmax |
|---|---|---|---|---|---|---|
| Mice | 50 mg/kg | p.o. | 2.6 h | 2637 ng/mL | 30240 ng·h/mL | 3.3 h |
| Rat | 25 mg/kg | p.o. | 4.7 h | 1063 ng/mL | 12241 ng·h/mL | 3.3 h |
RTx-303 (60 mg/kg, p.o., twice daily for 56 days), in combination with Olaparib, can prevent acquired resistance to PARPi in BRCA1-mutant tumors in MDA-MB-436 xenograft mice[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:For the BR-05-0566 (BR-05-0568) BRCA2 mutant PDX study, ∼ 30 mm3 tumor fragment was implanted subcutaneously into female BALB/c mice 6-8 weeks old[1].
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Dosage:60 mg/kg
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Administration:P.o., twice daily for 28 days (BR-05-0566) to 42 days (BR-05-0568)
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Result:BR-05-0566 model: Significantly inhibited tumor growth (compared to the vehicle group); combined with olaparib, it led to tumor regression; tumor volume reduction >80% in the combination group.
BR-05-0568 model: Combined with talazoparib, it resulted in 100% complete tumor elimination.
No significant weight loss was observed in any group.
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Animal Model:10 × 106 MDA-MB-436 (bearing BRCA1-Mutant) cells were injected with Matrigel subcutaneously into female BALB/c mice, 6-8 weeks old[1].
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Dosage:60 mg/kg
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Administration:P.o., twice daily for 56 days
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Result:Treated with Olaparib, tumors regressed rapidly and there was no recurrence.
1. This compound can be used as a tracer
2. This compound can be used as an internal standard for quantitative analysis by NMR, GC-MS, or LC-MS.
Chemical Information
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No. CAS 3035072-99-9
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Unlabeled Cas 3035072-66-0
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Peso molecular 569.49
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Fòrmula C24H22D3F7N4O4
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SMILES
CN(C)C[C@@H](O)CN(C1=O)CCN1C2=C(OC(N(C([2H])([2H])[2H])C3=CC=C(F)C=C3)=O)C(C(F)(F)F)=CC(C(F)(F)F)=C2
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureza y Documentación
Referencias
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
RTx-303 Related Classifications
HY-179219S Related Classifications
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