RLY-4008 free base · Synonyms: Lirafugratinib

RLY-4008 is a novel potent and highly selective FGFR2 inhibitor designed to overcome the emergence of on-target FGFR2 resistance mutations and…

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

Target FGFR

Research area Cancer

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Data Sheet SDS COA

RLY-4008 structure

CAS No.: 2549174-42-5

Download structure (.mol)

Pack sizes & pricing

Size	Price	SKU	Stock
50 mg	USD 450.00	BP-02029-50mg	In stock	Get quote
100 mg	USD 650.00	BP-02029-100mg	In stock	Get quote
250 mg	USD 950.00	BP-02029-250mg	In stock	Get quote
500 mg	USD 1,350.00	BP-02029-500mg	In stock	Get quote
1 g	USD 1,850.00	BP-02029-1g	In stock	Get quote

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Description

RLY-4008 is a novel potent and highly selective FGFR2 inhibitor designed to overcome the emergence of on-target FGFR2 resistance mutations and dose-limiting toxicities associated with current pan-FGFR inhibitors. RLY-4008 is > 200-fold selective over FGFR1, and > 80- and > 5000-fold selective over FGFR3 and FGFR4, respectively.

Biological activity

In Vitro Lirafugratinib (RLY-4008) has >250-fold selectivity over FGFR1, and >80- and >5,000-fold selectivity over FGFR3 and FGFR4, respectively. The reversible binding of Lirafugratinib promotes a rigid and extended P-loop in FGFR1 that disfavors covalent bond formation while minimally affecting the conformation of the P-loop in FGFR2, enabling efficient covalent bond formation and leading to FGFR2 selectivity. Lirafugratinib (24h) induces dose-dependent cleavage of caspase-3 and poly (ADP-ribose) polymerase (PARP)-early markers of apoptosis. Lirafugratinib (2h) demonstrates a dose-dependent reduction of phosphorylation of FGFR2 signaling pathway nodes, including FRS2, AKT, and ERK. RLY-4008 inhibits cellular proliferation with IC50<14 nM in FGFR2-dependent cell lines including KATO III, SNU-16 and NCI-H716, ICC13-7, and MFE-296, FGFR2N549K and AN3CA, FGFR2K310R; N549K and JHUEM-2, FGFR2C383R. In Vivo Lirafugratinib (RLY-4008; 1-30 mg/kg; orally, twice daily; 15-30 days) demonstrates antitumor activity in FGFR2-altered cancer xenograft models.

Identifiers

SMILES: C=C(C)C(NC1=CC=C(C2=C(C3=CC=C(OC4=NC=CC(C)=N4)C(F)=C3)C5=C(N)N=CN=C5N2C)C=C1)=O
InChIKey: XOQVZSSDIQQUGO-UHFFFAOYSA-N

Specifications

MW (average): 509.5343
Formula: C₂₈H₂₄FN₇O₂
CAS No.: 2549174-42-5
Physical state: Solid
Color: Off-white to light 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℃ 3 years; In solvent -20℃ 1 month;

Solubility

Soluble in DMSO 62.5 mg/mL

Documents

References

[1]. [1] Lescarbeau, Andre, et al. Preparation of substituted pyrrolopyrimidines as FGFR inhibitors and methods of making and using the same. WO2022109577.

Same target

Search FGFR

Same research area

Search Cancer