Dabogratinib (GMP) is the GMP-grade version of Dabogratinib (HY-159642). Dabogratinib (TYRA-300) is an orally active, selective FGFR3 inhibitor with an IC50 of 11 nM. Dabogratinib exhibits antitumor activity against urothelial carcinoma and solid tumors. Dabogratinib downregulates the FGFR3 and ERK1/2 signaling pathways, and induces tumor growth inhibition and regression in FGFR3-altered xenograft models. Dabogratinib promotes chondrocyte proliferation and differentiation, drives endochondral bone formation and overall body growth, partially restores long bone proportions, and improves craniofacial and spinal morphology. Dabogratinib can be used for the research of metastatic urothelial carcinoma, achondroplasia and hypochondroplasia.
For research use only. We do not sell to patients.
- CAS No.: 2800223-30-5
- Formula: C25H24Cl2N6O3S
- Molecular Weight:559.47
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biological Activity
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Chemical Information
- Protocols
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
Description
IC50 & Target
[3]|
FGFR3 11 nM (IC50) |
FGFR2 157 nM (IC50) |
FGFR1 278 nM (IC50) |
FGFR4 4045 nM (IC50) |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| DMS-114 | IC50 |
205 nM
Compound: 22
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Inhibition of cell viability in human DMS-114 cells harboring FGFR1-amplification incubated for 72 to 120 hrs by Cell Titer Glo assay
Inhibition of cell viability in human DMS-114 cells harboring FGFR1-amplification incubated for 72 to 120 hrs by Cell Titer Glo assay
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[PMID: 39258897] |
| KG-1 | IC50 |
109 nM
Compound: 22
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Inhibition of cell viability in human KG-1 cells harboring FGFR1-fusion incubated for 72 to 120 hrs by Cell Titer Glo assay
Inhibition of cell viability in human KG-1 cells harboring FGFR1-fusion incubated for 72 to 120 hrs by Cell Titer Glo assay
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[PMID: 39258897] |
| RT-4 | IC50 |
10 nM
Compound: 22
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Inhibition of cell viability in human RT-4 cells harboring FGFR3/TACC3 fusion incubated for 72 to 120 hrs by Cell Titer Glo assay
Inhibition of cell viability in human RT-4 cells harboring FGFR3/TACC3 fusion incubated for 72 to 120 hrs by Cell Titer Glo assay
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[PMID: 39258897] |
In Vitro
Dabogratinib (0.046 nM-3 μM; 2 h) (GMP) 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[1].
Dabogratinib (GMP) 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[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:RT112/84, RT112/84-V555M, and UM-UC-14 bladder cancer cell lines
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Concentration:0.046, 0.18, 0.73, 2.9, 12, 47, 188, 750, 3000 nM
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Incubation Time:2 hours
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Result:Induced a dose-dependent decrease in pERK1/2 levels in all three cell lines; showed similar dose-response patterns in gatekeeper-mutant RT112/84-V555M cell line as in RT112/84 and UM-UC-14 cell lines harboring only activating alterations.
In Vivo
Dabogratinib (12.5 mg/kg; p.o.; twice daily) (GMP) induces tumor regression in FGFR3::TACC3 fusion urothelial carcinoma xenograft models and FGFR3V555M urothelial carcinoma xenograft models[1].
Dabogratinib (8-14 mg/kg; p.o.; once daily; 4 weeks) (GMP) dose-dependently increases the growth rate of wild-type mice and promotes their long bone growth in vivo[2].
Dabogratinib (1.2 mg/kg; s.c.; once daily; 15 days) (GMP) promotes bone growth, improves skeletal proportions, optimizes growth plate structure, and increases the foramen magnum size in the Fgfr3Y367C/+ mouse model of achondroplasia (ACH)[2].
Dabogratinib (1.8 mg/kg; s.c.; once daily; 21 days) (GMP) increases bone length, enlarges foramen magnum size and improves intervertebral disc morphology in the Fgfr3N534K/+ mouse model of HCH[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:athymic nude (nu/nu) (female, 6 to 8 weeks old)[1]
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Dosage:3, 6 and 9 mg/kg (twice daily); 6, 12 and18 mg/kg (once daily)
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Administration:p.o.; twice daily; 21 days; p.o.; once daily; 21 days
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Result:Observed no tumor growth inhibition (TGI) at 3 mg/kg twice daily; Achieved 53% TGI at 6 mg/kg twice daily, 90% TGI at 9 mg/kg twice daily, 46% TGI at 6 mg/kg once daily, 80% TGI at 12 mg/kg once daily, and 96% TGI at 18 mg/kg once daily.
Detected significant tumor volume reduction with 12, 18 mg/kg once daily and 9 mg/kg twice daily compared with vehicle.
Observed more tumor regression with 18 mg/kg once daily than erdafitinib 12.5 mg/kg twice daily.
Recorded no body weight loss in any treatment group.
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Animal Model:C57BL/6J (female, 4-8 weeks of age)[2]
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Dosage:8, 10, 12, 14 mg/kg
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Administration:p.o.; once daily; 4 weeks
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Result:Increased nasoanal length by 7.3% with 14 mg/kg compared with vehicle; increased tibia length by 3.9% and femur length by 5.0% with 12 mg/kg compared with vehicle. Increased tibia length by 6.4% and femur length by 8.2% with 14 mg/kg compared with vehicle.
Induced significant increases in nasoanal length, tibia length, and femur length with 8 mg/kg and 10 mg/kg compared with vehicle.
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Animal Model:Tg-CMV^Cre/+ / Fgfr3^Y367C/+ (mixed male and female, 1 day of age, Achondroplasia modeling)[2]
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Dosage:1.2 mg/kg
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Administration:s.c.; once daily; 15 days
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Result:Increased nasoanal length by 17.88%, tail length by 25.10%, and body weight by 52.9% compared with vehicle-treated mutant mice; increased tibia length by 33.01%, femur length by 22.55%, ulna length by 23.51%, and humerus length by 15.52% compared with vehicle. Increased skull length by 10.08%, skull width by 3.74%, skull anteroposterior length by 8.92%, and skull nasio-occipital length by 7.87% compared with vehicle; increased foramen magnum transverse diameter by 13.05%, sagittal diameter by 9.28%, and area by 25.17% compared with vehicle. Improved the grade of skull base synchondroses, increased the size of hypertrophic zone chondrocytes (HZCs), increased proliferation of proliferating zone chondrocytes (PZCs), increased bone mineral density (BMD) by 21.4%, and increased bone volume-to-tissue volume ratio (BV/TV) by 73.3% compared with vehicle; increased L4-L6 lumbar vertebrae segment length by 23.49% compared with vehicle.
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Animal Model:Tg-CMV^Cre/+ / Fgfr3^N534K/+ (mixed male and female, 3 days of age, Hypochondroplasia modeling)[2]
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Dosage:1.8 mg/kg
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Administration:s.c.; once daily; 21 days
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Result:Increased femur length by 3.70%, tibia length by 3.75%, ulna length by 5.03%, and humerus length by 3.22% compared with vehicle-treated mutant mice.
Increased foramen magnum area by 7.51% and sagittal diameter by 6.35% compared with vehicle; reduced the grade of skull base synchondroses from grade V (completely fused) to grade IV (completely fused with cartilage margin remnants) in most mice and improved intervertebral disc shape compared with vehicle.
- Patient-Derived Xenograft (PDX)
- Patient-Derived Orthotopic Xenograft (PDOX)
- Splenic/Portal-Vein Liver Metastasis Xenograft
- Subcutaneous Cell-Line-Derived Xenograft
- Orthotopic Cell-Line Xenograft
- Intraperitoneal/Peritoneal Dissemination Xenograft
- Cell Viability Determination by MTT Colorimetric Assay
Clinical Trial
| NCT Number | Sponsor | Condition | Start Date |
Phase
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|---|---|---|---|---|
| NCT01329991 | Plexxikon| | 2011-05 | PHASE1 |
Chemical Information
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CAS No. 2800223-30-5
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Molecular Weight 559.47
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Formula C25H24Cl2N6O3S
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SMILES
O=S(N(C1)CC1(C2)CN2C(N=C3)=CC=C3C4=NNC5=CC=C(O[C@H](C)C6=C(Cl)C=NC=C6Cl)C=C54)(C)=O
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Synonyms
TYRA-300 (GMP)
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
[1]. Starrett JH, et al. Dabogratinib (TYRA-300), an FGFR3 isoform-selective inhibitor: preclinical and initial clinical evidence of anti-tumor activity. Mol Cancer Ther. Published online October 14, 2025. [Content Brief]
[2]. Starrett JH, et al. TYRA-300, an FGFR3-selective inhibitor, promotes bone growth in two FGFR3-driven models of chondrodysplasia. JCI Insight. 2025;10(9):e189307. Published 2025 Apr 3. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Dabogratinib (GMP) Related Classifications
HY-159642G Related Classifications
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