| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg | |||
| Other Sizes |
| Targets |
Target: Thrombopoietin receptor (TPO-R, also known as MPL, CD110). Hetrombopag is a small-molecule agonist that binds to the transmembrane domain of the TPO receptor, activating JAK2/STAT5 signaling pathways, which promotes proliferation and differentiation of megakaryocytes and increases platelet production. It mimics the action of endogenous thrombopoietin (TPO) but does not compete with TPO for binding.
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| ln Vitro |
In vitro, Hetrombopag is a potent TPO-R agonist. It increases the proliferation of TPO-R-dependent cell lines (e.g., BaF3/MPL) with EC50 values in the low nanomolar range. It activates JAK2/STAT5 phosphorylation in a concentration-dependent manner and promotes megakaryocyte differentiation from CD34+ hematopoietic stem cells, leading to increased platelet production in culture.
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| ln Vivo |
In vivo, Hetrombopag is orally active and effective in animal models of thrombocytopenia. In rodents, oral administration increases platelet counts in a dose-dependent manner. In clinical trials, Hetrombopag significantly increased platelet counts in patients with chronic ITP, with a high response rate (∼85-90%), and maintained durable platelet responses. It is also effective in severe aplastic anemia (SAA).
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| Enzyme Assay |
For cell-free TPO-R binding assays: membranes prepared from cells expressing human TPO receptor (MPL) are incubated with varying concentrations of Hetrombopag (0.1-1000 nM) and a radiolabeled TPO-R antagonist or fluorescent tracer. Binding affinity (KD) and IC50 are measured by radioligand displacement. Alternatively, competition binding assays with 125I-labeled TPO are used. No IC50/KD values have been published.
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| Cell Assay |
For cell-based assays: BaF3 cells stably expressing human TPO receptor (BaF3/MPL) are seeded in 96-well plates in IL-3-free medium (to avoid signal interference). Hetrombopag is added at varying concentrations (0.01-1000 nM) and cells are incubated for 48-72 h. Cell proliferation is measured by CCK-8, MTT, or Alamar Blue assay. EC50 values are calculated from dose-response curves. JAK2/STAT5 phosphorylation is measured by phospho-flow cytometry or Western blot. For megakaryocyte differentiation assays, human CD34+ hematopoietic stem cells are cultured with TPO and Hetrombopag for 10-14 days, and CD41+ and CD61+ megakaryocyte markers are analyzed by flow cytometry.
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| Animal Protocol |
For in vivo animal studies: for PK/PD studies, male Sprague-Dawley rats or CD-1 mice are orally administered Hetrombopag (1-10 mg/kg). Blood samples are collected at various time points for platelet count measurement and for plasma drug concentration analysis by LC-MS. For efficacy studies, a murine model of ITP (induced by anti-platelet antibody injection) is used. Mice are treated with Hetrombopag orally once daily for 7-14 days, and platelet counts are monitored. For the IND (Investigational New Drug) enabling studies, pharmacokinetics and toxicity studies were performed in rats and dogs prior to clinical trials.
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| ADME/Pharmacokinetics |
PK properties of Hetrombopag in humans: After oral administration, Tmax is 2-4 h, terminal half-life is 15-20 h, enabling once-daily dosing. Oral bioavailability is moderate (∼30-50%). Volume of distribution is moderate, and plasma protein binding is high (>95%). Metabolism is primarily via CYP1A2, CYP2C8, and CYP3A4, with glucuronidation as a secondary pathway. The compound and its metabolites are excreted in feces and urine. In rats, similar PK profiles with moderate clearance.
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| Toxicity/Toxicokinetics |
Toxicity profile: In clinical trials for ITP and SAA, Hetrombopag is generally well-tolerated. Common adverse effects (≥5%) include headache, fatigue, nausea, diarrhea, dizziness, and arthralgia. Serious adverse effects include hepatotoxicity (elevated ALT/AST) and thrombotic/thromboembolic events (portal vein thrombosis, DVT, PE). As with other TPO-RAs, there is a theoretical risk of progression of myelodysplastic syndromes (MDS) to acute myeloid leukemia (AML), but this has not been established. The compound is for research use only in this context (since the drug is approved, but labeled standard is for research).
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| References | |
| Additional Infomation |
Hetrombopag is being studied in the clinical trial NCT03976882 (Hetrombopag for the treatment of chemotherapy-induced thrombocytopenia in patients with malignant tumors).
Hetrombopag (trade name Herombopag, Hengqu, Hai Qu) is approved by the Chinese NMPA (National Medical Products Administration) for the treatment of immune thrombocytopenia (ITP) and severe aplastic anemia (SAA). It is not yet FDA-approved for use in the US (as of 2024-2025). The compound is also available as a stable isotope-labeled internal standard for bioanalytical method development and PK studies. It is a second-generation TPO-RA, structurally distinct from eltrombopag and avatrombopag. |
| Molecular Formula |
C25H22N4O5
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|---|---|
| Molecular Weight |
458.465985774994
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| Exact Mass |
458.16
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| Elemental Analysis |
C, 65.49; H, 4.84; N, 12.22; O, 17.45
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| CAS # |
2114365-78-3
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| PubChem CID |
135565610
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| Appearance |
Brown to dark brown solid powder
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| LogP |
5.4
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
34
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| Complexity |
860
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC1=C(C(=O)N(N1)C2=CC3=C(CCCC3)C=C2)N=NC4=CC=CC(=C4O)C5=CC=C(O5)C(=O)O
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| InChi Key |
YATJUTCKRWETAB-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C25H22N4O5/c1-14-22(24(31)29(28-14)17-10-9-15-5-2-3-6-16(15)13-17)27-26-19-8-4-7-18(23(19)30)20-11-12-21(34-20)25(32)33/h4,7-13,28,30H,2-3,5-6H2,1H3,(H,32,33)
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| Chemical Name |
5-[2-hydroxy-3-[[5-methyl-3-oxo-2-(5,6,7,8-tetrahydronaphthalen-2-yl)-1H-pyrazol-4-yl]diazenyl]phenyl]furan-2-carboxylic acid
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| Synonyms |
SHR8735; SHR 8735; SHR-8735; Hetrombopag
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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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
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.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *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). View More
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)] Oral Formulations
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). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1812 mL | 10.9058 mL | 21.8117 mL | |
| 5 mM | 0.4362 mL | 2.1812 mL | 4.3623 mL | |
| 10 mM | 0.2181 mL | 1.0906 mL | 2.1812 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.
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