| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
| Targets |
The primary target of Etavopivat is pyruvate kinase R (PKR), also known as pyruvate kinase isozymes R/L (PKLR). The compound is an allosteric activator of PKR. By activating PKR, Etavopivat enhances the glycolytic pathway in RBCs, leading to increased ATP production and decreased 2,3-DPG levels. This increases hemoglobin S oxygen affinity, reduces sickling, and improves RBC membrane deformability.
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| ln Vitro |
In vitro, Etavopivat activates PKR, leading to increased ATP levels and decreased 2,3-DPG levels in RBCs. This enhances the oxygen affinity of hemoglobin S and reduces sickling. The compound is a potent and selective activator of PKR.
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| ln Vivo |
In vivo, Etavopivat is orally bioavailable and has been shown to have anti-sickling effects. In clinical studies, the compound has demonstrated the ability to reduce sickling and improve RBC deformability. It is currently being investigated for the treatment of sickle cell disease.
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| Enzyme Assay |
The in vitro enzyme assay for Etavopivat involves measuring the activation of PKR. PKR is incubated with its substrates, phosphoenolpyruvate (PEP) and ADP, in the presence of the compound. The production of pyruvate is measured using a coupled enzyme assay, such as the lactate dehydrogenase (LDH) reaction, where the decrease in NADH absorbance is monitored at 340 nm. The compound's ability to activate PKR is quantified by measuring the increase in enzyme activity.
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| Cell Assay |
Cellular assays for Etavopivat typically involve the use of RBCs from healthy donors or patients with sickle cell disease. RBCs are treated with the compound, and ATP and 2,3-DPG levels are measured. The oxygen affinity of hemoglobin is assessed using oxygen dissociation curves. The compound's effects on RBC sickling and deformability are evaluated.
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| Animal Protocol |
In vivo animal studies for Etavopivat have been conducted in mouse models of sickle cell disease. The compound was administered orally, and its effects on hematological parameters, RBC sickling, and organ damage were assessed. The compound's ability to improve RBC survival and reduce disease severity was evaluated.
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| ADME/Pharmacokinetics |
Etavopivat is orally bioavailable. The compound is a small molecule that is likely to be well-absorbed and distributed. Detailed ADME parameters such as half-life, bioavailability, and tissue distribution are not fully available in the public domain. The compound is currently in clinical development.
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| Toxicity/Toxicokinetics |
Toxicity data for Etavopivat are not fully available in the public domain, but the compound is being investigated in clinical trials, suggesting an acceptable safety profile. As a research chemical, it is intended for laboratory use only and should be handled with standard safety precautions. Preclinical and clinical toxicity studies would be required for therapeutic development.
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| References |
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| Additional Infomation |
Etavopivat is a small-molecule erythrocyte pyruvate kinase (PKR) activator currently under investigation for its potential in treating sickle cell disease. Etavopivat is an orally administered small-molecule allosteric activator that activates selective erythrocyte (RBC) pyruvate kinase (PK-R) isoenzymes, potentially improving symptoms in patients with sickle cell disease (SCD). After oral administration of Etavopivat, it allosterically binds to and activates PK-R, thereby enhancing the activity of the glycolytic pathway in erythrocytes. This increases the level of adenosine triphosphate (ATP) in erythrocytes and decreases the level of 2,3-diphosphoglycerate (2,3-DPG). Ultimately, erythrocyte oxygen affinity is enhanced, deformability is improved, sickle cell hemolysis is reduced, hemoglobin (Hb) levels are increased, and erythrocyte membrane function is improved. Mutations in PK-R lead to PK-R deficiency, thereby preventing adequate erythrocyte glycolysis, resulting in the accumulation of the upstream glycolytic intermediate 2,3-DPG and a deficiency of the PK-R product ATP.
Etavopivat (FT-4202) (CAS#: 2245053-57-8) is a potent, selective, orally bioavailable red blood cell (RBC) pyruvate kinase (PKR) activator. It is a small-molecule allosteric activator that activates selective erythrocyte pyruvate kinase (PK-R) isoenzymes. Etavopivat is currently under investigation for its potential in treating sickle cell disease. It improves ATP levels and reduces 2,3-DPG levels in RBCs. |
| Molecular Formula |
C22H23N3O6S
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|---|---|
| Molecular Weight |
457.4995
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| Exact Mass |
457.13
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| CAS # |
2245053-57-8
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| Related CAS # |
(Rac)-Etavopivat;2622070-93-1
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| PubChem CID |
135338378
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| Appearance |
White to off-white solid powder
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| LogP |
-0.8
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
32
|
| Complexity |
832
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| Defined Atom Stereocenter Count |
1
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| SMILES |
S(C1C([H])=NC2=C(C=1[H])OC([H])([H])C([H])([H])O2)(N1C([H])([H])C2C([H])([H])N(C([C@@]([H])(C3C([H])=C([H])C([H])=C([H])C=3[H])C([H])([H])O[H])=O)C([H])([H])C=2C1([H])[H])(=O)=O
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| InChi Key |
KZFFYEPYCVDOGE-LJQANCHMSA-N
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| InChi Code |
InChI=1S/C22H23N3O6S/c26-14-19(15-4-2-1-3-5-15)22(27)24-10-16-12-25(13-17(16)11-24)32(28,29)18-8-20-21(23-9-18)31-7-6-30-20/h1-5,8-9,19,26H,6-7,10-14H2/t19-/m1/s1
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| Chemical Name |
(2S)-1-[5-(2,3-dihydro-[1,4]dioxino[2,3-b]pyridin-7-ylsulfonyl)-1,3,4,6-tetrahydropyrrolo[3,4-c]pyrrol-2-yl]-3-hydroxy-2-phenylpropan-1-one
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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: 50 mg/mL (109.29 mM)
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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 | 2.1858 mL | 10.9290 mL | 21.8579 mL | |
| 5 mM | 0.4372 mL | 2.1858 mL | 4.3716 mL | |
| 10 mM | 0.2186 mL | 1.0929 mL | 2.1858 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.
Link: https://clinicaltrials.gov/ct2/show/NCT06612268
Conditions:Sickle Cell DiseaseLink: https://clinicaltrials.gov/ct2/show/NCT06198712
Conditions:Sickle Cell DiseaseLink: https://clinicaltrials.gov/ct2/show/NCT05725902
Conditions:Sickle Cell Disease
Title:A Study of Etavopivat in Adults and Adolescents With Sickle Cell Disease (HIBISCUS)
Status:Active, not recruiting
updateDate:2026-04-06
Ctid:NCT04624659
Link: https://clinicaltrials.gov/ct2/show/NCT04624659
Conditions:Sickle Cell DiseaseLink: https://clinicaltrials.gov/ct2/show/NCT07023029
Conditions:Healthy Volunteers|Sickle Cell Disease|ThalassemiaLink: https://clinicaltrials.gov/ct2/show/NCT06581627
Conditions:Healthy Volunteers|Sickle Cell Disease|ThalassemiaLink: https://clinicaltrials.gov/ct2/show/NCT04987489
Conditions:Sickle Cell Disease|ThalassemiaLink: https://clinicaltrials.gov/ct2/show/NCT05568225
Conditions:Very Low Risk, Low Risk, or Intermediate Risk MDS Per IPSS-RLink: https://clinicaltrials.gov/ct2/show/NCT06336018
Conditions:Liver DiseasesLink: https://clinicaltrials.gov/ct2/show/NCT06433661
Conditions:Healthy Volunteers Sickle Cell Disease, ThalassemiaLink: https://clinicaltrials.gov/ct2/show/NCT06813924
Conditions:Healthy Volunteers Sickle Cell Disease, ThalassemiaLink: https://clinicaltrials.gov/ct2/show/NCT05953584
Conditions:Sickle Cell DiseaseProducts are for research use only; We do not sell to patients
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