BiochemProbe — Life Science Research Reagents

TYRA-300 free base · Synonyms: TYRA 300 · TYRA300

TYRA-300 is an FGFR3-selective inhibitor agnostic to the gatekeeper mutation, with less hyperphosphatemia mediated by FGFR1 inhibition than pan-FGFR…

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

Target FGFR ERK
Research area Metabolic Disease Cancer
Purity >98% Stock Inquire

TYRA-300 structure

CAS No.: 2800223-30-5

Download structure (.mol)

Pack sizes & pricing

Size Price SKU Stock
100 mg USD 580.00 BP-00906-100mg In stock Get quote
250 mg USD 928.00 BP-00906-250mg In stock Get quote
500 mg USD 1,328.00 BP-00906-500mg In stock Get quote
1 g Inquire BP-00906-1g In stock Inquire

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Description

TYRA-300 is an FGFR3-selective inhibitor agnostic to the gatekeeper mutation, with less hyperphosphatemia mediated by FGFR1 inhibition than pan-FGFR inhibitors in preclinical models.

Biological activity

In Vitro Dabogratinib (0.046 nM-3 μM; 2 h) induces dose-dependent downregulation of the FGFR3 downstream signaling pathway (assessed by pERK1/2 levels) in RT112/84, RT112/84-V555M and UM-UC-14 bladder cancer cell lines. Dabogratinib inhibits the viability of FGFR3-driven bladder cancer cell lines, with IC50 values of 9 nM for the RT112/84 cell line, 17 nM for the RT112/84-V555M cell line, and 16 nM for the UM-UC-14 cell line. In Vivo Dabogratinib (3-18 mg/kg; p.o.; twice/once daily; 21 days) exhibits dose-dependent in vivo efficacy in urothelial carcinoma xenograft models harboring FGFR3S249C. Dabogratinib (12.5 mg/kg; p.o.; twice daily) induces tumor regression in FGFR3::TACC3 fusion urothelial carcinoma xenograft models and FGFR3V555M urothelial carcinoma xenograft models. Dabogratinib (8-14 mg/kg; p.o.; once daily; 4 weeks) dose-dependently increases the growth rate of wild-type mice and promotes their long bone growth in vivo. Dabogratinib (1.2 mg/kg; s.c.; once daily; 15 days) promotes bone growth, improves skeletal proportions, optimizes growth plate structure, and increases the foramen magnum size in the Fgfr3Y367C/+ mouse model of achondroplasia (ACH). Dabogratinib (1.8 mg/kg; s.c.; once daily; 21 days) increases bone length, enlarges foramen magnum size and improves intervertebral disc morphology in the Fgfr3N534K/+ mouse model of HCH.

Identifiers

SMILES
C[C@@H](OC1=CC2=C(NN=C2C2=CC=C(N=C2)N2CC3(C2)CN(C3)S(C)(=O)=O)C=C1)C1=C(Cl)C=NC=C1Cl
InChIKey
JOAFWIHZEBKYQK-OAHLLOKOSA-N

Specifications

MW (average)
559.4670
Formula
C25H24Cl2N6O3S
CAS No.
2800223-30-5
Physical state
Solid
Color
white to off-white
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 4℃ 2 years; In solvent -20℃ 1 month;

Solubility

Soluble in DMSO

References

[1]. Hudkins RL, et al., Discovery of TYRA-300: First Oral Selective FGFR3 Inhibitor for the Treatment of Urothelial Cancers and Achondroplasia. J Med Chem. 2024 Sep 26;67(18):16737-16756.
[2]. Starrett, J. et al., 462P TYRA-300: FGFR3 selective and gatekeeper agnostic. Annals of Oncology, Volume 33, S751

Same target

Search FGFR

Same research area

Search Metabolic Disease