Synonym
SHR8735; SHR 8735; SHR-8735; Hetrombopag
IUPAC/Chemical Name
(E)-5-(2-hydroxy-3-(2-(3-methyl-5-oxo-1-(5,6,7,8-tetrahydronaphthalen-2-yl)-1,5-dihydro-4H-pyrazol-4-ylidene)hydrazinyl)phenyl)furan-2-carboxylic acid
InChi Key
BDGGFTDRPHKXFC-HPNDGRJYSA-N
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/h4,7-13,26,30H,2-3,5-6H2,1H3,(H,32,33)/b27-22+
SMILES Code
O=C(C1=CC=C(C2=CC=CC(N/N=C3C(N(C4=CC=C5CCCCC5=C4)N=C/3C)=O)=C2O)O1)O
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
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 Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO
Shelf Life
>3 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
Biological target:
Hetrombopag is an orally active human thrombopoietin receptor agonist that protects cardiomyocyte survival from oxidative stress damage as an enhancer of stem cells.
In vitro activity:
Accordingly, the effect of hetrombopag on megakaryopoiesis in TPOR‐positive human CB‐derived CD34+ cells, used as a source of hematopoietic stem cells, was investigated. Hetrombopag stimulated the proliferation of human CB‐derived CD34+ cells, with an EC50 value of 2.3 nmol/L. The total number of MK (CD41+) increased after treated with hetrombopag n a concentration‐dependent manner, with an EC50 value of 4.5 nmol/L. The percentage of mature MK (CD41+/CD42a+) also increased after treatment with hetrombopag. As expected, hetrombopag stimulated MK proplatelet formation from human CB‐CD34+ cells in vitro. Corresponding to its MK‐stimulating activity, hetrombopag induced a concentration‐dependent increase in the phosphorylation of STAT3, STAT5 and ERK1/2 in human CB CD34+ cells, exerting a much stronger effect than eltrombopag. Taken together, these results suggest that hetrombopag is capable of stimulating the proliferation and differentiation of megakaryocyte progenitor cells, and then proplatelet production via TPOR signalling.
Reference: J Cell Mol Med. 2018 Nov;22(11):5367-5377. https://pubmed.ncbi.nlm.nih.gov/30156363/
In vivo activity:
A once‐daily dosing regimen in nude mice subcutaneously implanted with hollow fibres containing 32D‐MPL cells was used to investigate the efficacy of hetrombopag in vivo. Daily oral administration of 18 mg/kg hetrombopag for 12 days significantly stimulated proliferation and prevented apoptosis of 32D‐MPL cells in hollow fibres in a time‐dependent manner. The number of 32D‐MPL cells reached a maximum after 3 days of daily oral administration of hetrombopag, and then decreased within 12 days. In contrast, few live cells were present in hollow fibres in the vehicle group after 3 days of treatment. The in vivo efficacy of hetrombopag was also dose‐dependent, and was significant at doses of 6 mg/kg or greater (P < 0.01).
Reference: J Cell Mol Med. 2018 Nov;22(11):5367-5377. https://pubmed.ncbi.nlm.nih.gov/30156363/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
0.0 |
0.00 |
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
458.47
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
1. Xie C, Zhao H, Bao X, Fu H, Lou L. Pharmacological characterization of hetrombopag, a novel orally active human thrombopoietin receptor agonist. J Cell Mol Med. 2018 Nov;22(11):5367-5377. doi: 10.1111/jcmm.13809. Epub 2018 Aug 29. PMID: 30156363; PMCID: PMC6201220.
2. Chen T, Chen Z, Zhang S, Zhang K, Wang L. Development and validation of a LC-MS/MS method for quantification of hetrombopag for pharmacokinetics study. Springerplus. 2015 Oct 29;4:652. doi: 10.1186/s40064-015-1446-0. PMID: 26543786; PMCID: PMC4628022.
In vitro protocol:
1. Xie C, Zhao H, Bao X, Fu H, Lou L. Pharmacological characterization of hetrombopag, a novel orally active human thrombopoietin receptor agonist. J Cell Mol Med. 2018 Nov;22(11):5367-5377. doi: 10.1111/jcmm.13809. Epub 2018 Aug 29. PMID: 30156363; PMCID: PMC6201220.
2. Chen T, Chen Z, Zhang S, Zhang K, Wang L. Development and validation of a LC-MS/MS method for quantification of hetrombopag for pharmacokinetics study. Springerplus. 2015 Oct 29;4:652. doi: 10.1186/s40064-015-1446-0. PMID: 26543786; PMCID: PMC4628022.
In vivo protocol:
1. Xie C, Zhao H, Bao X, Fu H, Lou L. Pharmacological characterization of hetrombopag, a novel orally active human thrombopoietin receptor agonist. J Cell Mol Med. 2018 Nov;22(11):5367-5377. doi: 10.1111/jcmm.13809. Epub 2018 Aug 29. PMID: 30156363; PMCID: PMC6201220.
1: Xie C, Zhao H, Bao X, Fu H, Lou L. Pharmacological characterization of hetrombopag, a novel orally active human thrombopoietin receptor agonist. J Cell Mol Med. 2018 Nov;22(11):5367-5377. doi: 10.1111/jcmm.13809. Epub 2018 Aug 29. PubMed PMID: 30156363; PubMed Central PMCID: PMC6201220.
2: Zheng L, Liang MZ, Zeng XL, Li CZ, Zhang YF, Chen XY, Zhu X, Xiang AB. Safety, Pharmacokinetics and Pharmacodynamics of Hetrombopag Olamine, a Novel TPO-R Agonist, in Healthy Individuals. Basic Clin Pharmacol Toxicol. 2017 Nov;121(5):414-422. doi: 10.1111/bcpt.12815. Epub 2017 Jun 22. PubMed PMID: 28544774.
3: Zhou N, Wang J, Li X, Zhao Y, Sun Y, Zou C. Hetrombopag, a Thrombopoietin Receptor Agonist, Protects Cardiomyocyte Survival from Oxidative Stress Damage as an Enhancer of Stem Cells. Cardiovasc Drugs Ther. 2016 Dec;30(6):567-577. PubMed PMID: 27838864.
4: Chen T, Chen Z, Zhang S, Zhang K, Wang L. Development and validation of a LC-MS/MS method for quantification of hetrombopag for pharmacokinetics study. Springerplus. 2015 Oct 29;4:652. doi: 10.1186/s40064-015-1446-0. eCollection 2015. PubMed PMID: 26543786; PubMed Central PMCID: PMC4628022.
