| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 100mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
Avatrombopag targets the thrombopoietin receptor (TPO-R), also known as MPL. This receptor is a member of the hematopoietic cytokine receptor superfamily and is expressed on megakaryocytes and their progenitors. By binding to and activating the TPO-R, avatrombopag mimics the action of endogenous thrombopoietin, stimulating JAK/STAT signaling pathways that promote megakaryocyte proliferation and differentiation, ultimately increasing platelet production.
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| ln Vitro |
In vitro, avatrombopag acts as a thrombopoietin receptor agonist, stimulating the proliferation of TPO-R-dependent cell lines. It demonstrates potent activity in megakaryocyte differentiation assays, promoting the formation of mature megakaryocytes from progenitor cells. Specific EC50 values for receptor activation or cell proliferation are not detailed in the available sources. The compound is a non-peptide agonist, offering advantages over peptide-based TPO mimetics.
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| ln Vivo |
50% effective concentration values for cell proliferation with AS1670542 or eltrombopag were 1.9 and 13nM, respectively, while those for megakaryocyte colony formation from human cord blood CD34(+) cells with AS1670542 or eltrombopag were 260 and 950nM, respectively. On Day 14 after the start of administration, AS1670542 significantly increased the number of human platelets in non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice with transplanted human hematopoietic stem cells at 0.3 (P<0.05); in contrast, while administration of eltrombopag also increased the numbers of these platelets at 30mg/kg/day (P=0.058), no statistical significance was noted in the increase. Here, we identified AS1670542, a novel orally-active TPO receptor agonist which mimics the biological activity of TPO and may demonstrate greater in vitro and in vivo pharmacologically efficacy than eltrombopag.[1]
we examined the in vivo platelet-increasing effect of AKR-501 in human platelet producing non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice transplanted with human fetal liver CD34(+) cells. Daily oral administration of AKR-501 dose-dependently increased the number of human platelets in these mice, with significance achieved at doses of 1 mg/kg and above. The peak unbound plasma concentrations of AKR-501 after administration at 1 mg/kg in NOD/SCID mice were similar to those observed following administration of an active oral dose in human subjects. These results suggest that AKR-501 is an orally-active TPO receptor agonist that may be useful in the treatment of patients with thrombocytopenia.[2] In vivo, avatrombopag is orally active and increases platelet counts in animal models and humans. It has been evaluated in clinical trials for the treatment of thrombocytopenia in patients with chronic liver disease and chronic immune thrombocytopenia. The compound is approved by the FDA for these indications. Specific animal model data are not detailed in the available sources beyond its clinical efficacy. |
| Enzyme Assay |
The thrombopoietin receptor binding assay for avatrombopag involves incubating the compound with membrane preparations from cells expressing the human TPO-R and a radiolabeled TPO ligand. After incubation, bound and free ligands are separated by filtration, and the radioactivity is counted. The IC50 for displacement of the radioligand is calculated. Functional agonism is assessed using a cell proliferation assay in TPO-R-dependent cell lines or by measuring STAT5 phosphorylation.
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| Cell Assay |
To evaluate the cellular activity of avatrombopag, TPO-R-dependent cell lines (such as UT-7/TPO or Ba/F3-TPO-R cells) are seeded in 96-well plates and treated with varying concentrations of avatrombopag. Cell proliferation is measured using an MTT or CellTiter-Glo assay after 48-72 hours of treatment. The EC50 for stimulation of cell proliferation is calculated. STAT5 phosphorylation can be assessed by Western blot or phospho-specific ELISA as a measure of pathway activation.
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| Animal Protocol |
The in vivo efficacy of avatrombopag is evaluated in animal models of thrombocytopenia, such as chemotherapy-induced thrombocytopenia models in mice or rats. Animals are treated with a myelosuppressive agent to induce thrombocytopenia, followed by administration of avatrombopag orally at various doses. Platelet counts are measured in blood samples collected at regular intervals. The compound's ability to increase platelet counts is expressed as the percentage increase relative to vehicle-treated controls.
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| ADME/Pharmacokinetics |
Avatrombopag is orally bioavailable with a pharmacokinetic profile that supports once-daily dosing. Specific pharmacokinetic parameters (e.g., Cmax, Tmax, half-life, AUC) are not detailed in the available sources. The compound has a molecular weight of 649.7 and a molecular formula of C29H34Cl2N6O3S2·C4H4O4. It is a small molecule with properties suitable for oral administration.
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| Toxicity/Toxicokinetics |
Avatrombopag is generally well-tolerated, with common adverse effects including headache, fatigue, and nausea. As a thrombopoietin receptor agonist, it carries a risk of thrombosis in patients with underlying risk factors. The compound is approved by the FDA for the treatment of thrombocytopenia in patients with chronic liver disease and chronic immune thrombocytopenia. Specific toxicity data from preclinical studies are not detailed in the available sources.
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| References |
:Eur J Pharmacol.2011 Jan10;650(1):58-63;Eur J Haematol.2009 Apr;82(4):247-54. |
| Additional Infomation |
Avatrombopag maleate is the maleate form of Avatrombopag, an orally potent thrombopoietin receptor (TPOR; MPL) agonist with potential megakaryocyte-stimulating activity. Upon administration, Avatrombopag binds to TPOR and stimulates its activity, which may lead to the proliferation and differentiation of bone marrow progenitor cells into megakaryocytes. This can increase platelet production and may prevent chemotherapy-induced thrombocytopenia (CIT). TPOR is a cytokine receptor belonging to the hematopoietin receptor superfamily.
See also: Avatrombopag (containing the active fraction). Drug IndicationsDoppler is indicated for the treatment of severe thrombocytopenia in adult patients with chronic liver disease scheduled for invasive surgery. Doppler is indicated for the treatment of primary chronic immune thrombocytopenic purpura (ITP) in adults who have not responded to other treatments, such as corticosteroids and immunoglobulins. Treatment of idiopathic thrombocytopenic purpura (ITP) and secondary thrombocytopenic purpura in patients with liver disease. Avatrombopag maleate is an orally active, non-peptide thrombopoietin receptor agonist. It is approved for the treatment of thrombocytopenia in patients with chronic liver disease undergoing a procedure and for patients with chronic immune thrombocytopenia. The compound stimulates the proliferation and differentiation of megakaryocytes, leading to increased platelet production. |
| Molecular Formula |
C29H34CL2N6O3S2
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|---|---|
| Molecular Weight |
649.65
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| Exact Mass |
764.162
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| CAS # |
677007-74-8
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| Related CAS # |
Avatrombopag;570406-98-3;Avatrombopag hydrochloride;570403-17-7
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| PubChem CID |
9918581
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| Appearance |
White to off-white solid powder
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| LogP |
6.745
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
14
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
50
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| Complexity |
1050
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| Defined Atom Stereocenter Count |
0
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| SMILES |
ClC1=CC(=CN=C1N1CCC(C(=O)O)CC1)C(NC1=NC(C2=CC(=CS2)Cl)=C(N2CCN(CC2)C2CCCCC2)S1)=O.OC(/C=C\C(=O)O)=O
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| Synonyms |
YM477; YM-477; YM 477; AKR501; AKR 501; AKR-501; E5501; E 5501; E-5501; AS 1670542; AS1670542; AS-1670542
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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:≥ 30 mg/mL
Water:< 1 mg/mL
Ethanol:< 1 mg/mL
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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 | 1.5393 mL | 7.6965 mL | 15.3929 mL | |
| 5 mM | 0.3079 mL | 1.5393 mL | 3.0786 mL | |
| 10 mM | 0.1539 mL | 0.7696 mL | 1.5393 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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