| Size | Price | Stock | Qty |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| Other Sizes |
| Targets |
CSF1R (IC50 = 8 nM); c-KIT (IC50 = 14 nM); PDGFRβ; PDGFRα
Seralutinib targets multiple receptor tyrosine kinases involved in pulmonary vascular remodeling. The compound inhibits PDGFRα and PDGFRβ, which are key drivers of smooth muscle cell proliferation and migration in the pulmonary arteries. Seralutinib also targets CSF1R with an IC50 of 8 nM and c-KIT with an IC50 of 14 nM. Inhibition of these kinases reduces the proliferation of pulmonary artery smooth muscle cells, attenuates vascular remodeling, and decreases pulmonary vascular resistance. The compound's ability to target multiple kinases involved in PAH pathogenesis makes it a potentially more effective therapy than agents targeting a single pathway. The inhaled route of administration allows for high local concentrations in the lung while minimizing systemic exposure. |
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| ln Vitro |
In vitro, seralutinib demonstrates potent inhibition of its target kinases. The compound inhibits PDGFR-mediated signaling pathways, including downstream effectors such as AKT and ERK, which are involved in cell survival and proliferation. Seralutinib inhibits the proliferation of pulmonary artery smooth muscle cells stimulated by PDGF. The compound also inhibits CSF1R and c-KIT with low nanomolar IC50 values. In cellular assays, seralutinib shows good selectivity for its intended targets with minimal off-target activity. The compound's potency and selectivity profile support its development as a targeted therapy for PAH.
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| ln Vivo |
Seralutinib (GB002) (treated respiratory, inhaled) significantly lowered right ventricular systolic pressure and mean pulmonary artery pressure. In Seralutinib (GB002)-treated mice, hemodynamic alterations were accompanied by reduced muscularization of pulmonary arterioles and lobar Seralutinib (GB002) was well tolerated [1]. GB002-mediated suppression of lung PDGFRα/β phosphorylation after adsorption to healthy Sprague Dawley [2]. Seralutinib is dose- and time-regulated. Induces lung BMPR2 protein expression [2].
In vivo, seralutinib demonstrates significant efficacy in preclinical models of pulmonary arterial hypertension. In a rat model of PAH induced by monocrotaline pneumonectomy, seralutinib (2.5 mg/kg) administered via passive inhalation prevents increases in pulmonary artery systolic pressure. Two-week treatment with seralutinib delivered by inhalation significantly reduces right ventricular systolic pressure and mean pulmonary artery pressure. The compound also attenuates pulmonary vascular remodeling, reducing medial wall thickness and improving vascular function. Seralutinib improves right ventricular function and survival in PAH models. These preclinical findings support the clinical development of seralutinib for PAH. |
| Enzyme Assay |
Seralutinib's inhibitory activity is measured using biochemical kinase assays. Recombinant kinases (PDGFRα, PDGFRβ, CSF1R, c-KIT) are incubated with the test compound, ATP, and a peptide substrate. Phosphorylation of the substrate is detected using HTRF or luminescence-based detection methods. IC50 values are calculated from dose-response curves. Selectivity profiling is performed by screening seralutinib against a panel of kinases to assess off-target inhibition. These biochemical assays are essential for characterizing the potency and selectivity of seralutinib.
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| Cell Assay |
Seralutinib is tested on cultured pulmonary artery smooth muscle cells (PASMCs) and other relevant cell types. PASMCs are stimulated with PDGF in the presence or absence of seralutinib; proliferation is assessed by BrdU incorporation or cell counting; migration is evaluated using scratch wound or Boyden chamber assays; signaling pathway inhibition is assessed by Western blot for phosphorylated PDGFR, AKT, and ERK. These cell-based assays provide mechanistic insights into the antiproliferative and anti-migratory effects of seralutinib on vascular cells.
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| Animal Protocol |
Seralutinib is evaluated in the monocrotaline-induced PAH rat model and other preclinical models. In these models, seralutinib is administered via inhalation (passive or active delivery) at various doses for 2-4 weeks. Hemodynamic parameters including right ventricular systolic pressure, mean pulmonary artery pressure, and cardiac output are measured; right ventricular hypertrophy is assessed by the Fulton index; pulmonary vascular remodeling is evaluated by histomorphometry; survival is monitored. These in vivo studies provide evidence for the efficacy of seralutinib in PAH.
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| ADME/Pharmacokinetics |
Pharmacokinetic studies of seralutinib have been conducted in preclinical species. The compound is administered via inhalation, achieving high local concentrations in the lung with low systemic exposure. This pharmacokinetic profile is advantageous for PAH therapy, as it allows for potent inhibition of pulmonary vascular targets while minimizing systemic side effects. The half-life, clearance, and volume of distribution of seralutinib have been characterized. The compound's pharmacokinetic properties support once- or twice-daily inhalation dosing.
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| Toxicity/Toxicokinetics |
Preclinical toxicity studies indicate that seralutinib is well-tolerated at therapeutic doses. The inhaled route of administration minimizes systemic exposure, reducing the risk of systemic toxicities commonly associated with TKIs. Local tolerability in the lung has been evaluated, with no significant adverse effects on pulmonary function or airway inflammation reported at therapeutic doses. The safety profile of seralutinib is consistent with that of other TKIs, with off-target effects minimized by the compound's selectivity and targeted delivery.
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| References |
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| Additional Infomation |
Seralutinib (GB002, PK-10571) is an inhaled PDGFRα/β inhibitor in clinical development for pulmonary arterial hypertension. The compound has shown efficacy in preclinical models and is being evaluated in clinical trials for PAH. Seralutinib's novel mechanism of action—targeting multiple kinases involved in pulmonary vascular remodeling—represents a promising new approach to PAH therapy. The inhaled route of administration allows for targeted delivery to the lungs, potentially improving the therapeutic index compared to systemically administered TKIs. Seralutinib is also being investigated for other fibrotic and proliferative diseases. Clinical trials are ongoing to evaluate the safety, tolerability, and efficacy of seralutinib in patients with PAH.
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| Molecular Formula |
C27H27N5O3
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|---|---|
| Molecular Weight |
469.545
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| Exact Mass |
469.211
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| Elemental Analysis |
C, 69.07; H, 5.80; N, 14.92; O, 10.22
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| CAS # |
1619931-27-9
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| Related CAS # |
1619931-27-9
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| PubChem CID |
91663352
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| Appearance |
White to light yellow solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
601.4±55.0 °C at 760 mmHg
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| Flash Point |
317.5±31.5 °C
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| Vapour Pressure |
0.0±1.7 mmHg at 25°C
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| Index of Refraction |
1.649
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| LogP |
3.01
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
35
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| Complexity |
667
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| Defined Atom Stereocenter Count |
1
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| SMILES |
O(C)C1=C(C=CC(=C1)C1=CN=CC(=N1)N[C@@H](C)C1C=CC=C(C=1)NC(C1C=NC=C(C)C=1)=O)OC
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| InChi Key |
JHJNPOSPVGRIAN-SFHVURJKSA-N
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| InChi Code |
InChI=1S/C27H27N5O3/c1-17-10-21(14-28-13-17)27(33)31-22-7-5-6-19(11-22)18(2)30-26-16-29-15-23(32-26)20-8-9-24(34-3)25(12-20)35-4/h5-16,18H,1-4H3,(H,30,32)(H,31,33)/t18-/m0/s1
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| Chemical Name |
N-[3-[(1S)-1-[[6-(3,4-dimethoxyphenyl)pyrazin-2-yl]amino]ethyl]phenyl]-5-methylpyridine-3-carboxamide
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| Synonyms |
Seralutinib; PK-10571; GB002; PK10571; GB-002; PK 10571; GB 002
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: 94~200 mg/mL (200.2~425.96 mM)
Ethanol: ~94 mg/mL (~200.2 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 5.75 mg/mL (12.25 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 57.5 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.32 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (5.32 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1297 mL | 10.6485 mL | 21.2970 mL | |
| 5 mM | 0.4259 mL | 2.1297 mL | 4.2594 mL | |
| 10 mM | 0.2130 mL | 1.0648 mL | 2.1297 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT05934526 | Recruiting | Drug: Placebo Drug: Seralutinib |
Pulmonary Arterial Hypertension | GB002, Inc. | September 30, 2023 | Phase 3 |
| NCT04816604 | Recruiting | Drug: GB002 (seralutinib) Device: Generic Dry Powder Inhaler |
Pulmonary Arterial Hypertension | GB002, Inc., a wholly owned subsidiary of Gossamer Bio, Inc. |
April 5, 2021 | Phase 2 |
| NCT04456998 | Completed | Drug: GB002 (seralutinib) Drug: Placebo |
Pulmonary Artery Hypertension | GB002, Inc., a wholly owned subsidiary of Gossamer Bio, Inc. |
November 12, 2020 | Phase 2 |
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