RP-2119 free base · Synonyms: RP 2119 · RP2119

RP-2119 is an orally bioactive Polymerase Theta inhibitor.

For research use only. Not for human or veterinary use.

Target DNA/RNA Synthesis

Research area Cancer

Purity >98% Stock Inquire

Data Sheet SDS COA

RP-2119 structure

CAS No.: 2922287-81-6

Download structure (.mol)

Pack sizes & pricing

Size	Price	SKU	Stock
5 mg	USD 498.00	BP-02060-5mg	In stock	Get quote
10 mg	USD 798.00	BP-02060-10mg	In stock	Get quote
25 mg	USD 1,298.00	BP-02060-25mg	In stock	Get quote
50 mg	USD 1,998.00	BP-02060-50mg	In stock	Get quote
100 mg	USD 2,898.00	BP-02060-100mg	In stock	Get quote
500 mg	Inquire	BP-02060-500mg	In stock	Inquire

Need another size or custom synthesis? Request a quote.

Description

RP-2119 is an orally bioactive Polymerase Theta (Polθ) inhibitor, with an IC50 of 0.7 nM against human Polθ ATPase. RP-2119 reduces Polθ activity and exerts antiproliferative effects in BRCA2-deficient cancer cells. RP-2119 exhibits antitumor activity in BRCA2-deficient cancer cell xenograft mouse models. RP-2119 can be used for the research of cancer and homologous recombination-deficient cancers, including brca1/brca2-mutant cancers and shld2-mutant cancers.

Biological activity

In Vitro RP-2119 potently inhibits human Polθ ATPase activity in the ADP-Glo biochemical assay, with an IC50 of 0.7 nM. It also inhibits Polθ ATPase activity in mice, rats, dogs, pigs and chimpanzees, with IC50 values ranging from <1.5 nM to <5 nM in the ADP-Glo biochemical assay. RP-2119 binds to Polθ in K562 cells expressing the ePL-tagged Flag-Polθ helicase domain, with an EC50 of 82 nM in the CETSA assay. RP-2119 (for 12-14 days) potently inhibits the proliferation of DLD-1, HCT 116 and DOTC24510 BRCA2-/- cells, with EC50 values of 45, 51 and 266 nM. RP-2119 inhibits Polθ-mediated MMEJ activity in DLD-1 cells carrying Cas9/sgRNA-induced double-strand breaks at the AAVS1 locus, with an IC50 of 54 nM. In Vivo RP-2119 (Compound 113) (0-300 mg/kg; p.o.; once/twice daily; throughout the entire study period/24 days) induces dose-dependent tumor growth inhibition in a mouse HCT116 BRCA2-/- colorectal cancer model, with a maximum inhibition rate of 53%, and enhances the tumor volume reduction effect of Olaparib. RP-2119 (45 mg/kg; p.o.; once daily; for the entire study duration) enhances the tumor volume reduction effect of Carboplatin in a mouse DLD1 BRCA2-/- colorectal cancer model. Combination treatment with RP-2119 (45 mg/kg; p.o.; twice daily; up to 50 days) and Olaparib induces tumor regression in the BRCA2-mutant mouse HBCx-10 breast cancer PDX model, with significantly enhanced efficacy compared to Olaparib monotherapy.

Identifiers

SMILES: O=C(C1=C(C=C(N=C1)C2=NN(C=C2)C)C3=CC(C(F)F)=NC=C3OC)NC4=NN=C(S4)C#CC5CC5
InChIKey: GSOUEPGHLLFNOU-UHFFFAOYSA-N

Specifications

MW (average): 507.5150
Formula: C₂₄H₁₉F₂N₇O₂S
CAS No.: 2922287-81-6
Physical state: Solid
Color: Off-white to yellow
Shipping: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage: Powder -20°C, 3 years , 4°C, 2 years; In solvent -20°C, 1 month.

Solubility

Soluble in DMSO : 100 mg/mL

Documents

References

[1]. Bingcan Liu, et al. N-(5-substituted-[(I,3,4-thiadiazolyl) or(I,3-thiazolyl)](substituted)carboxamide compoundspharmaceutical compositions, and methods of preparing the amide compounds and of their use. Wo2024069592A1.2024.04.04.

[2]. Mochirian P, et al. The Discovery of RP-2119: A Potent, Selective, and Orally Bioavailable Polθ ATPase Inhibitor. J Med Chem. 2025;68(18):19726-19745.

Same target

Search DNA/RNA Synthesis

Same research area

Search Cancer