[CAS NO. 570403-17-7] Avatrombopaghydrochloride
PRODUCTS SPECIFICATIONS [570403-17-7]
DESCRIPTION [570403-17-7]
Overview
| MDL | - |
|---|---|
| Molecular Weight | 686.12 |
| Molecular Formula | C29H35Cl3N6O3S2 |
| SMILES | O=C(C1CCN(C2=NC=C(C(NC3=NC(C4=CC(Cl)=CS4)=C(N5CCN(C6CCCCC6)CC5)S3)=O)C=C2Cl)CC1)O.Cl |
2 Publications Citing Use of MCE
Summary
Avatrombopag (AKR-501) hydrochloride is an orally active, nonpeptide thrombopoietin (TPO) receptor agonist ( EC 50 =3.3 nM). Avatrombopag hydrochloride mimics the biological activities of TPO. Avatrombopag hydrochloride increases platelet production by activating the intracellular signaling system, and promotes production of platelets and megakaryocytes from hemopoietic precursor cells. Avatrombopag hydrochloride is a substrate of cytochrome P450 (CYP) 2C9 and CYP3A [1] [2] [3] .
In Vitro
Avatrombopag (E5501; AKR-501) hydrochloride specifically targets the TPO receptor and stimulated megakaryocytopoiesis throughout the development and maturation of megakaryocytes just as recombinant human TPO (rhTPO) did. Avatrombopag hydrochloride is showed to have effect in humans and chimpanzees only
[1]
.
Avatrombopag hydrochloride (0-100 nM) supports the proliferation of TPO receptor expressing Ba/F3 cell in a concentration-dependent fashion. Avatrombopag hydrochloride (0-3 μM) induces tyrosine phosphorylation of STAT3 and STAT5, and threonine phosphorylation of ERK in the cells, as did rhTPO
[1]
.
Avatrombopag hydrochloride promotes megakaryocyte colony formation from human CB CD34
+
cells in a concentration-dependent fashion. The EC
50
is 25 nM for Avatrombopag hydrochloride and the maximum activity of Avatrombopag hydrochloride is similar to that of rhTPO
[1]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
Avatrombopag hydrochloride (0.3-3 mg/kg; p.o.; daily for 14 days) increases the number of human platelets in NOD/SCID mice transplanted with human FL CD34 + cells [1] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
| Animal Model: | NOD/SCID mice (transplanted with human FL CD34+cells) [1] |
| Dosage: | 0.3, 1, and 3 mg/kg |
| Administration: | P.o.; daily for 14 days |
| Result: | Dose-dependently increased the number of human platelets, resulting in approximately a 2.7‐fold increase at 1 mg/kg/d and a 3.0-fold increase at 3 mg/kg/d on day 14 after the start of administration. |
Clinical Trial
| NCT Number | Sponsor | Condition | Start Date | Phase |
|---|---|---|---|---|
| NCT01260155 | Eisai Inc. |
Healthy Subjects
|
January 2010 | Phase 1 |
| NCT04312789 | Ayman Saad|Sobi, Inc.|Ohio State University Comprehensive Cancer Center |
Platelet Disorder
|
December 2022 | Phase 2 |
| NCT05218226 | Institute of Hematology & Blood Diseases Hospital|Tianjin Medical University Cancer Institute and Hospital|Tianjin Medical University Second Hospital|Tianjin Third Central Hospital|Tianjin People´s Hospital|Henan Cancer Hospital|The Second Affiliated Hospital of Kunming Medical University |
Chemotherapy-induced Thrombocytopenia|Avatrombopag
|
January 25, 2022 | Phase 2 |
| NCT00441090 | Eisai Inc. |
Chronic Idiopathic Thrombocytopenic Purpura|Purpura, Thrombocytopenic, Idiopathic
|
February 2007 | Phase 2 |
| NCT04516967 | Sobi, Inc. |
Immune Thrombocytopenia
|
March 2, 2021 | Phase 3 |
| NCT04993885 | Institute of Hematology & Blood Diseases Hospital |
Immune Thrombocytopenia|Autoantibodies|Evan Syndrome|Connective Tissue Diseases
|
September 1, 2021 | Phase 4 |
| NCT05046327 | Sobi, Inc. |
Immune Thrombocytopenia
|
October 14, 2021 | Phase 3 |
| NCT01759394 | Eisai Inc. |
Healthy Volunteers
|
October 2012 | Phase 1 |
| NCT04638829 | Sobi, Inc. |
Immune Thrombocytopenia
|
March 15, 2021 | Phase 4 |
| NCT01549054 | Eisai Inc. |
Idiopathic Thrombocytopenic Purpura
|
January 2012 | Phase 1 |
| NCT05518331 | Institute of Hematology & Blood Diseases Hospital|Peking University People´s Hospital|Xiyuan Hospital of China Academy of Chinese Medical Sciences|Second Hospital of Shanxi Medical University|First Affiliated Hospital of Harbin Medical University|The First Hospital of Hebei Medical University |
Refractory Aplastic Anemia
|
June 1, 2022 | Not Applicable |
| NCT01355289 | Eisai Inc. |
Thrombocytopenia
|
November 2011 | Phase 2 |
| NCT03471078 | Sobi, Inc. |
Chemotherapy-induced Thrombocytopenia
|
October 12, 2018 | Phase 3 |
| NCT04609891 | Anhui Provincial Cancer Hospital |
Thrombocytopenia
|
May 26, 2020 | Not Applicable |
| NCT04896528 | Peking Union Medical College Hospital |
Thrombocytopenia|Avatrombopag
|
June 6, 2021 | Phase 2 |
| NCT05571332 | Institute of Hematology & Blood Diseases Hospital |
Aplastic Anemia
|
June 28, 2022 | Not Applicable |
| NCT02227693 | Eisai Co., Ltd.|Eisai Inc. |
Thrombocytopenia Associated With Chronic Liver Disease
|
July 2014 | Phase 2 |
| NCT04728789 | Peking Union Medical College Hospital |
Aplastic Anemia|Drug Effect
|
February 1, 2021 | Phase 2|Phase 3 |
| NCT04931849 | University of Rochester |
Thrombocytopenia
|
May 6, 2022 | Early Phase 1 |
| NCT04943042 | Swedish Orphan Biovitrum |
Immune Thrombocytopenia|ITP
|
February 22, 2022 | |
| NCT01289509 | Eisai Inc. |
Idiopathic Thrombocytopenia Purpura
|
December 2010 | Phase 1 |
| NCT05087459 | Shanghai Zhongshan Hospital |
Thrombocytopenia
|
June 30, 2021 | |
| NCT04915287 | Chinese PLA General Hospital |
Thrombocytopenia; Drugs|Chronic Liver Disease
|
June 6, 2021 | Phase 4 |
| NCT03554759 | Sobi, Inc. |
Thrombocytopenia
|
July 2, 2018 | |
| NCT00914927 | Eisai Inc. |
Thrombocytopenia Related to Chronic Liver Disease
|
May 2009 | Phase 2 |
| NCT05382013 | Third Affiliated Hospital, Sun Yat-Sen University |
Thrombocytopenia|Hepatitis B, Chronic|Acute-On-Chronic Liver Failure
|
April 27, 2022 | Phase 4 |
| NCT05369208 | Sobi, Inc. |
Immune Thrombocytopenia
|
June 15, 2022 | Phase 3 |
| NCT05433922 | Institute of Hematology & Blood Diseases Hospital |
Severe Aplastic Anemia
|
June 1, 2022 | Not Applicable |
| NCT02809768 | Eisai Inc. |
Healthy Participants
|
April 2016 | Phase 1 |
| NCT02039076 | Eisai Inc. |
Thrombocytopenia
|
December 2013 | Phase 1 |
| NCT04949009 | Shandong University |
Primary Immune Thrombocytopenia
|
March 1, 2021 | |
| NCT05143892 | The First Affiliated Hospital of Soochow University |
Platelet Disorder
|
December 1, 2021 | Phase 2 |
| NCT01251731 | Eisai Inc. |
Healthy Subjects
|
July 2010 | Phase 1 |
| NCT04906083 | Tongji Hospital|Anhui Provincial Hospital|The First Affiliated Hospital of Nanchang University|Taihe Hospital, Hubei University of Medicine|The First Hospital of Jilin University |
Liver Failure|Thrombocytopenia|Decompensated Cirrhosis
|
February 1, 2021 | Phase 4 |
| NCT01327872 | Eisai Inc. |
Purpura, Thrombocytopenic, Idiopathic|Acute Idiopathic Thrombocytopenic Purpura|Chronic Thrombocytopenia
|
February 2011 | Phase 1 |
| NCT01976104 | Eisai Inc. |
Thrombocytopenia Associated With Liver Disease
|
November 2013 | Phase 3 |
| NCT03326843 | Sobi, Inc. |
Thrombocytopenia
|
March 26, 2018 | Phase 3 |
| NCT04437953 | Memorial Sloan Kettering Cancer Center|Sobi, Inc. |
Thrombocytopenia|Cancer|Liver Diseases
|
May 27, 2020 | Phase 2 |
| NCT04797182 | Sun Yat-sen University |
Thrombocytopenia|Cytarabine Causing Adverse Effects in Therapeutic Use|Lymphoma
|
April 2021 | Phase 2 |
| NCT01437384 | Eisai Inc. |
Idiopathic Thrombocytopenic Purpura (ITP)
|
September 2011 | Phase 1 |
| NCT01438840 | Eisai Inc. |
Chronic Thrombocytopenia|Immune Thrombocytopenia
|
February 16, 2012 | Phase 3 |
| NCT01774773 | Eisai Co., Ltd.|Eisai Inc. |
Healthy
|
January 2013 | Phase 1 |
| NCT01972529 | Eisai Inc. |
Thrombocytopenia Associated With Liver Disease
|
February 2014 | Phase 3 |
| NCT01433978 | Eisai Inc. |
Idiopathic Thrombocytopenic Purpura
|
March 26, 2012 | Phase 3 |
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
4°C, sealed storage, away from moisture
* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
Solvent & Solubility
DMSO : 8.33 mg/mL ( 12.14 mM ; ultrasonic and warming and heat to 60°C)
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 1.4575 mL | 7.2874 mL | 14.5747 mL |
| 5 mM | 0.2915 mL | 1.4575 mL | 2.9149 mL |
| 10 mM | 0.1457 mL | 0.7287 mL | 1.4575 mL |
-
1.
Add each solvent one by one: 10% DMSO >> 90% (20% SBE-β-CD in saline)
Solubility: ≥ 0.83 mg/mL (1.21 mM); Clear solution
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.