Dabogratinib (TYRA-300) is a selective inhibitor of fibroblast growth factor receptor 3 (FGFR3). In kinase activity assays, it demonstrated selectivity for FGFR3 over FGFR1 (63-fold), FGFR2 (19-fold), and FGFR4 (55-fold). [2]
In cellular assays, dabogratinib showed IC50 values of 9 nM in RT112/84 cells (FGFR3:TACC3 fusion), 17 nM in RT112/84-V555M cells (gatekeeper resistance mutation), and 16 nM in UM-UC-14 cells (FGFR3 S249C mutation). [2]
In chondrodysplasia models, TYRA-300 targets FGFR3 gain-of-function mutations (G380R in achondroplasia and N540K in hypochondroplasia). [1]

Dabogratinib (TYRA-300) treatment resulted in a dose-dependent decrease in the level of pERK1/2 in three bladder cancer cell lines: RT112/84 (FGFR3:TACC3 fusion), RT112/84-V555M (gatekeeper mutation V555M on FGFR3:TACC3 fusion), and UM-UC-14 (FGFR3 S249C mutation). The pharmacodynamic effect was assessed by automated capillary electrophoresis for protein separation followed by immunoassay-based detection. A similar dose-response was observed for the gatekeeper-mutant cell line as for the two cell lines harboring only the activating alterations. [2]
Cellular IC50 values for dabogratinib were 9 nmol/L in RT112/84, 17 nmol/L in RT112/84-V555M, and 16 nmol/L in UM-UC-14. [2]
TYRA-300 in chondrodysplasia models: In wild-type C57BL/6J mice, TYRA-300 treatment (14 mg/kg once daily oral) increased nasoanal length by 7.3%, tibia length by 6.4%, and femur length by 8.2% compared to vehicle. Significant increases were also observed at 8, 10, and 12 mg/kg doses. [1]
In Fgfr3Y367C/+ mice (ACH model), TYRA-300 (1.2 mg/kg subcutaneous daily for 15 days starting at day 1) increased nasoanal length by 17.88%, tail length by 25.10%, body weight by 52.9%, tibia length by 33.01%, femur length by 22.55%, ulna length by 23.51%, and humerus length by 15.52%. Histological analysis showed improved organization of proliferative zone chondrocytes, increased secondary ossification center bone volume (+21.4% BMD, +73.3% BV/TV), increased collagen type X staining, and increased PCNA staining. [1]
In Fgfr3N534K/+ mice (HCH model), TYRA-300 (1.8 mg/kg subcutaneous daily for 21 days starting at day 3) increased femur length by 3.70%, tibia by 3.75%, ulna by 5.03%, and humerus by 3.22%. pERK1/2-positive cells were significantly decreased after treatment. [1]

Dabogratinib (TYRA-300) treatment resulted in a dose-dependent decrease in the level of pERK1/2 in three bladder cancer cell lines: RT112/84 (FGFR3:TACC3 fusion), RT112/84-V555M (gatekeeper mutation V555M on FGFR3:TACC3 fusion), and UM-UC-14 (FGFR3 S249C mutation). The pharmacodynamic effect was assessed by automated capillary electrophoresis for protein separation followed by immunoassay-based detection. A similar dose-response was observed for the gatekeeper-mutant cell line as for the two cell lines harboring only the activating alterations. [2]
Cellular IC50 values for dabogratinib were 9 nmol/L in RT112/84, 17 nmol/L in RT112/84-V555M, and 16 nmol/L in UM-UC-14. [2]
TYRA-300 in chondrodysplasia models: In wild-type C57BL/6J mice, TYRA-300 treatment (14 mg/kg once daily oral) increased nasoanal length by 7.3%, tibia length by 6.4%, and femur length by 8.2% compared to vehicle. Significant increases were also observed at 8, 10, and 12 mg/kg doses. [1]
In Fgfr3Y367C/+ mice (ACH model), TYRA-300 (1.2 mg/kg subcutaneous daily for 15 days starting at day 1) increased nasoanal length by 17.88%, tail length by 25.10%, body weight by 52.9%, tibia length by 33.01%, femur length by 22.55%, ulna length by 23.51%, and humerus length by 15.52%. Histological analysis showed improved organization of proliferative zone chondrocytes, increased secondary ossification center bone volume (+21.4% BMD, +73.3% BV/TV), increased collagen type X staining, and increased PCNA staining. [1]
In Fgfr3N534K/+ mice (HCH model), TYRA-300 (1.8 mg/kg subcutaneous daily for 21 days starting at day 3) increased femur length by 3.70%, tibia by 3.75%, ulna by 5.03%, and humerus by 3.22%. pERK1/2-positive cells were significantly decreased after treatment. [1]

Dabogratinib (TYRA-300) kinase activity assays and selectivity profiling were previously reported (Hudkins et al., J. Med. Chem. 2024). Crystal structures demonstrated its ability to bind FGFR3 agnostic to the gatekeeper mutation residue. [2]
No detailed enzyme assay protocols are described in the provided articles. [1,2]

Dabogratinib (TYRA-300) Western blot analysis: RT112/84 and UM-UC-14 cells were seeded at 100,000 cells per well in 96-well plates and allowed to adhere overnight. Cells were treated with vehicle control (DMSO) or dabogratinib starting at 3 μmol/L and serially diluted fourfold for eight additional doses in duplicate. Cells were incubated at 37°C and 5% CO2 for 2 hours. After treatment, cells were washed once with PBS and lysed in cold Bicine CHAPS lysis buffer supplemented with protease and phosphatase inhibitors for 20 minutes. pERK1/2 was used at 1:50 dilution, and tERK1/2 and β-actin were used at 1:100 dilution. Data analysis was performed using Compass for Simple Western v6.1. AUC values for pERK and tERK were reported from the molecular weight chemiluminescence signal at 44 kDa spanning ±10%. Dabogratinib treatment resulted in a dose-dependent decrease in pERK1/2 levels in all three cell lines. [2]
Cell lines were cultured as follows: RT112/84 cells in RPMI-1640 media supplemented with 10% FBS; UM-UC-14 cells in minimum essential medium supplemented with 10% FBS, 1× GlutaMAX, and 1× nonessential amino acids. All cells were cultured at 37°C and 5% CO2. Cells were routinely tested monthly for Mycoplasma contamination. [2]

Dabogratinib (TYRA-300) UM-UC-14 xenograft model: The human tumor cell line UM-UC-14 was mixed 1:1 with Matrigel and injected subcutaneously into the flank of female athymic nude (nu/nu) mice (8 × 10⁶ cells per mouse). When tumors were established, mice were randomized to treatment groups according to tumor volume. Dabogratinib and erdafitinib were formulated in 30% hydroxypropyl-β-cyclodextrin and administered orally. Tumor sizes were measured using calipers [tumor volume (mm³) = (a × b²)/2, where a = length and b = width] two or three times weekly. Body weights were also measured two or three times weekly. Treatment lasted 21 days. [2]
TYRA-300 Wild-type mouse growth velocity study: Female C57BL/6J mice (3 weeks old) were measured for nasoanal length and nasotal length under anesthesia. At 28 days of age, mice were randomized to treatment groups of 12 mice per group according to nasoanal length. TYRA-300 was dissolved in 30% hydroxypropyl-β-cyclodextrin for oral gavage administration once daily for 4 weeks. Nasoanal lengths and body weights were monitored once weekly, along with daily clinical observations. Tibias and femurs were collected and measured with calipers at study end. [1]
TYRA-300 Pharmacokinetic study: C57BL/6J mice were randomized according to body weight. A mixture of female and male mice was used. Depending on age, 3-8 mice per group were dosed with a single subcutaneous dose of TYRA-300 (1.2 mg/kg). Blood was collected either serially at 3 different time points (if ≥4 weeks old) or terminally at a single time point (if 1-3 weeks old). Plasma was harvested using lithium heparin tubes at 0.5, 1, 4, 6, 8, 12, and 24 hours after dosing. Compound concentration was detected using liquid chromatography with tandem mass spectrometry. [1]
TYRA-300 Fgfr3Y367C/+ mouse model (ACH): Tg-CMVCre/+/Fgfr3Y367C/+ mice were tattooed and assigned to treatment groups at 1 day of age. TYRA-300 was dissolved in aqueous HCl (3.5 mM) containing 5% DMSO and administered subcutaneously at 1.2 mg/kg for 15 days. Vehicle was administered to wild-type (n=10) or Fgfr3Y367C/+ mice (n=10). Clinical observations, nasoanal length, and tail length measurements were performed every 3 days, and body weights were collected daily. [1]
TYRA-300 Fgfr3N534K/+ mouse model (HCH): Tg-CMVCre/+/Fgfr3N534K/+ mice were tattooed and assigned to treatment groups at 3 days of age. TYRA-300 was dissolved in aqueous HCl (3.5 mM) containing 5% DMSO and administered subcutaneously at 1.8 mg/kg for 21 days. Vehicle was administered to wild-type (n=12) or Fgfr3N534K/+ mice (n=11). [1]

TYRA-300 Pharmacokinetic profile in juvenile mice: Following a single subcutaneous dose of 1.2 mg/kg, plasma levels were measured in male and female C57BL/6J mice aged 1 to 12 weeks. In 1-week-old mice, AUCinf was 1,789 h•ng/mL with Cmax of 287 ng/mL. In 2-week-old mice, AUCinf was 2,295 h•ng/mL. In 3- to 12-week-old mice, average AUCinf was 538 h•ng/mL, about 3.8 times lower than in 1- and 2-week-old mice. The higher exposure in younger mice may be explained by incomplete development of cytochrome P450 enzymes until at least 3 weeks of age. [1]
The pharmacokinetic profile of TYRA-300 in adult rats was previously described (Hudkins et al., J. Med. Chem. 2024). [1]
No human pharmacokinetic data are reported in the provided articles. [1,2]

Dabogratinib (TYRA-300) In the UM-UC-14 xenograft model, no body weight loss was observed in any of the treatment groups at doses up to 18 mg/kg QD or 9 mg/kg BID. [2]
In the SURF301 phase I clinical trial (NCT05544552), preliminary safety data showed a very low frequency of grade 3 treatment-related adverse events. In three case reports: Case 1 (84-year-old female, 90 mg QD reduced to 60 mg QD) experienced grade 2 peripheral sensory neuropathy deemed possibly related; no grade ≥3 treatment-related AEs. Case 2 (64-year-old male, 90 mg QD) had no grade ≥3 AEs related to study drug. Case 3 (67-year-old female, 120 mg QD reduced to 90 mg QD) experienced grade 2 AST elevation deemed possibly related; no grade ≥3 AEs. [2]
TYRA-300 In wild-type mouse growth velocity study, there was no difference in body weight among treatment groups at doses of 12 and 14 mg/kg oral QD. [1]
In Fgfr3Y367C/+ and Fgfr3N534K/+ mouse models, no adverse effects or body weight loss were reported at subcutaneous doses of 1.2 mg/kg and 1.8 mg/kg, respectively. [1]

[1]. TYRA-300, an FGFR3-selective inhibitor, promotes bone growth in two FGFR3-driven models of chondrodysplasia. JCI Insight. 2025;10(9):e189307.
[2]. Dabogratinib (TYRA-300), an FGFR3 isoform-selective inhibitor: preclinical and initial clinical evidence of anti-tumor activity. Mol Cancer Ther. 2026 Mar 2;25(3):408-415.

Dabogratinib (TYRA-300) is being developed for the treatment of FGFR3-altered metastatic urothelial carcinoma and other solid tumors, as well as for achondroplasia and hypochondroplasia. [1,2]
The SURF301 study (NCT05544552) is a phase I/II, open-label, international, multicenter dose-escalation and -expansion trial of dabogratinib monotherapy in adults with FGFR3-altered advanced or metastatic urothelial carcinoma and other solid tumors. At the time of publication, dosages through 100 mg once daily were cleared. The optimal dabogratinib monotherapy dosage is yet to be established. [2]
In the SURF301 study, preliminary efficacy data demonstrated six confirmed partial responses in 11 (54.5%) FGFR3-altered mUC efficacy-evaluable patients at dosages ≥90 mg once daily. [2]
Three case reports from the SURF301 study: Case 1 (FGFR3 S249C mutation) had a partial response with -55% change at 5.1 weeks and -64% at 15.7 weeks, maintained response for 12.6 months. Case 2 (FGFR3::JAKMIP1 fusion) had partial response with -33% change at 7.3 weeks and -49% at 15.7 weeks, maintained response for 7.4 months. Case 3 (FGFR3::TACC3 fusion) had partial response with -46.2% change at 7.4 weeks and -49.8% at 15.4 weeks, maintained response for 12 months. All three patients remained on treatment after progression due to continuous clinical benefit. [2]
TYRA-300 In Fgfr3Y367C/+ mice, treatment improved the size and shape of the skull and foramen magnum, which has clinical implications for foramen magnum stenosis in achondroplasia. It also increased lumbar vertebrae length and improved intervertebral disc shape. [1]
Mechanistically, TYRA-300 increased both proliferation and differentiation of chondrocytes in the growth plate. [1]

C25H24CL2N6O3S

559.47

558.10076

C, 53.67; H, 4.32; Cl, 12.67; N, 15.02; O, 8.58; S, 5.73

2800223-30-5

170647464

Typically exists as solids at room temperature

3.6

1

8

6

37

916

1

JOAFWIHZEBKYQK-OAHLLOKOSA-N

InChI=1S/C25H24Cl2N6O3S/c1-15(23-19(26)9-28-10-20(23)27)36-17-4-5-21-18(7-17)24(31-30-21)16-3-6-22(29-8-16)32-11-25(12-32)13-33(14-25)37(2,34)35/h3-10,15H,11-14H2,1-2H3,(H,30,31)/t15-/m1/s1

5-[(1R)-1-(3,5-dichloro-4-pyridinyl)ethoxy]-3-[6-(2-methylsulfonyl-2,6-diazaspiro[3.3]heptan-6-yl)-3-pyridinyl]-1H-indazole

TYRA-300; Dabogratinib; TYRA 300; 2800223-30-5; TYRA300; A1AV2; (R)-5-(1-(3,5-Dichloropyridin-4-yl)ethoxy)-3-(6-(6-(methylsulfonyl)-2,6-diazaspiro[3.3]heptan-2-yl)pyridin-3-yl)-1H-indazole; .

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO: ~100 mg/mL (178.7 mM)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)