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Purity: ≥98%
Avatrombopag (formerly AKR-501, YM-477, AS-1670542; E-5501; trade name: Doptelet) is an orally-active small molecule thrombopoietin (TPO) receptor agonist that was used for the first time in 2008 to treat patients with chronic idiopathic thrombocytopenic purpura. Thrombopoietin (TPO) is the principal physiologic regulator of platelet production. As of May 2018, Eltrombopag was approved by US FDA to treat low blood platelet count (thrombocytopenia) in adults with chronic liver disease who are scheduled to undergo a medical or dental procedure. AKR-501 specifically targeted the TPO receptor and stimulated megakaryocytopoiesis throughout the development and maturation of megakaryocytes just as rhTPO did. AKR-501, however, was shown to be effective only in humans and chimpanzees with high species specificity.
| ln Vitro |
As with recombinant human TPO (rhTPO), avatrombopag (E5501; AKR-501) specifically binds the TPO receptor and induces megakaryopoiesis throughout megakaryocyte development and maturation [1]. In a concentration-dependent way, avatrombopag (0-100 nM) promotes the growth of Ba/F3 cells that express TPO receptors. Similar to rhTPO, avatrombopag (0-3 μM) causes tyrosine phosphorylation of STAT3 and STAT5, as well as threonine phosphorylation of ERK, in cells [1]. In human CD34+ cells, avatrombopag stimulates the development of megakaryocyte colonies in a concentration-dependent way. Avatrombopag has a 25 nM EC50 and a maximal activity that is comparable to rhTPO [1].
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| ln Vivo |
NOD/SCID mice transplanted with human FL CD34+ cells have higher human platelet counts when administered with avatrombopag (0.3-3 mg/kg; oral; daily for 14 days) [1].
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| Cell Assay |
Cell proliferation assay [1]
Cell Types: Ba/F3 cells Tested Concentrations: 0.003 μM, 0.03 μM, 0.3 μM, 3 μM Incubation Duration: Experimental Results: Increased proliferation of Ba/F3 cells expressing TPO receptor in a concentration-dependent manner. Western Blot Analysis [1] Cell Types: Ba/F3 cells Tested Concentrations: 0.003 μM, 0.03 μM, 0.3 μM, 3 μM Incubation Duration: 15 minutes Experimental Results: Induction of intracellular tyrosine phosphorylation of STAT3 and STAT5 and threonine of ERK Acid phosphorylation. |
| Animal Protocol |
Animal/Disease Models: NOD/SCID (severe combined immunodeficient) mouse (transplanted with human FL CD34+ cells) [1]
Doses: 0.3, 1, and 3 mg/kg Route of Administration: Po; one time/day for 14 days Experimental Results: Human platelet counts were dose-dependent The increase was approximately 2.7-fold at 1 mg/kg/d and approximately 3.0-fold at 3 mg/kg/d on day 14 after initiation of administration. |
| References |
[1]. Fukushima-Shintani M, et al. AKR-501 (YM477) a novel orally-active thrombopoietin receptor agonist. Eur J Haematol. 2009;82(4):247-254.
[2]. Xu H, et al. Avatrombopag for the treatment of thrombocytopenia in patients with chronic liver disease. Expert Rev Clin Pharmacol. 2019 Sep;12(9):859-865. [3]. Nomoto M, et al. Pharmacokinetic/pharmacodynamic drug-drug interactions of avatrombopag when coadministered with dual or selective CYP2C9 and CYP3A interacting drugs. Br J Clin Pharmacol. 2018;84(5):952-960. |
| Molecular Formula |
C29H34CL2N6O3S2
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| Molecular Weight |
649.65
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| CAS # |
570406-98-3
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| Related CAS # |
Avatrombopag hydrochloride;570403-17-7;Avatrombopag maleate;677007-74-8
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| SMILES |
O=C(C1CCN(C2=NC=C(C(NC3=NC(C4=CC(Cl)=CS4)=C(N5CCN(C6CCCCC6)CC5)S3)=O)C=C2Cl)CC1)O
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| Chemical Name |
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| 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) |
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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.
 AKR‐501 specifically acts on human Thrombopoietin (TPO) receptor.Eur J Haematol.2009 Apr;82(4):247-54. |
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 AKR‐501 promotes megakaryocyte differentiation from human CD34+cells.
AKR‐501 activates STAT5 in human and chimpanzee platelets, but not in baboon, rhesus, and cynomolgus monkey platelets.Eur J Haematol.2009 Apr;82(4):247-54. |
 AKR‐501 induces polyploidization of megakaryocytes.
Oral administration of AKR‐501 increases the number of human platelets in NOD/SCID mice transplanted with human FL CD34+cells.Eur J Haematol.2009 Apr;82(4):247-54. |
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