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Purity: ≥98%
Acalabrutinib (formerly known as ACP196; ACP-196; trade name: Calquence) is a selective second-generation Bruton's tyrosine kinase (BTK) inhibitor with anticancer activity. By blocking the B-cell antigen receptor (BCR) signaling pathway from being activated, it works. Adults with mantle cell lymphoma were given FDA approval to receive acalabrutinib in 2017. Mantle cell lymphoma and chronic lymphocytic leukemia/small lymphocytic leukemia are two non-Hodgkin lymphoma types that can be treated with it. Due to the decreased intrinsic reactivity of ACP-196's electrophile, a previous study demonstrated that ACP-196 had high selectivity for Btk when tested against a panel of 395 non-mutant kinases. ACP-196, in contrast to ibrutinib, was unable to inhibit EGFR, Itk, or Txk. Further verification of ibrutinib's EGFR inhibition without ACP-196 inhibition was obtained through phosphoflow assays conducted on EGFR-expressing cell lines.
| Targets |
BTK (IC50 = 3 nM)
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|---|---|
| ln Vitro |
Acalabrutinib inhibits tyrosine phosphorylation of downstream targets of ERK, IKB, and AKT in the in vitro signaling assay on primary human CLL cells. IC50 values on nine kinases with a cysteine residue in the same location as BTK show that acalabrutinib has a higher selectivity for BTK. Crucially, acalabrutinib does not inhibit EGFR, ITK, or TEC like ibrutinib does. EGFR phosphorylation at tyrosine residues Y1068 and Y1773 is unaffected by acalabrutinib. Acalabrutinib exhibits nearly no inhibition or a much higher IC50 (>1000 nM) on the kinase activities of ITK, EGFR, ERBB2, ERBB4, JAK3, BLK, FGR, FYN, HCK, LCK, LYN, SRC, and YES1 when compared to ibrutinib[1].
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| ln Vivo |
ACP-196, when given orally to mice, inhibits anti-IgM-induced CD86 expression in CD19+ splenocytes in a dose-dependent manner; the ED50 for ACP-196 is 0.34 mg/kg, while that of ibrutinib is 0.91 mg/kg. The length of Btk inhibition following a single oral dose of 25 mg/kg is compared using a comparable model. At three hours after dosage, ACP-196 inhibits CD86 expression by more than 90%[3].
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| Enzyme Assay |
ACP-196's decreased intrinsic reactivity of its electrophile was linked to its high selectivity for Btk when tested against a panel of 395 non-mutant kinases, according to a previous study. In contrast to ibrutinib, ACP-196 was unable to inhibit EGFR, Itk, or Txk. Further confirmation of ibrutinib's EGFR inhibition without ACP-196 inhibition was obtained through phosphoflow assays conducted on EGFR-expressing cell lines.
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| Cell Assay |
the EGFR-expressing cell lines used in the phosphoflow tests EGFR inhibition by ibrutinib was further validated without any ACP-196 inhibition being seen.
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| Animal Protocol |
canine model of B cell NHL
2.5, 5, 10 mg/kg. orally administered |
| References |
| Molecular Formula |
C26H23N7O2
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|---|---|---|
| Molecular Weight |
465.51
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| Exact Mass |
465.19
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| Elemental Analysis |
C, 67.08; H, 4.98; N, 21.06; O, 6.87
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| CAS # |
1420477-60-6
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| Related CAS # |
Acalabrutinib-d4;2699608-18-7;Acalabrutinib-d3
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| Appearance |
Yellow solid powder
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| SMILES |
CC#CC(=O)N1CCC[C@H]1C2=NC(=C3N2C=CN=C3N)C4=CC=C(C=C4)C(=O)NC5=CC=CC=N5
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| InChi Key |
WDENQIQQYWYTPO-IBGZPJMESA-N
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| InChi Code |
InChI=1S/C26H23N7O2/c1-2-6-21(34)32-15-5-7-19(32)25-31-22(23-24(27)29-14-16-33(23)25)17-9-11-18(12-10-17)26(35)30-20-8-3-4-13-28-20/h3-4,8-14,16,19H,5,7,15H2,1H3,(H2,27,29)(H,28,30,35)/t19-/m0/s1
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| Chemical Name |
4-[8-amino-3-[(2S)-1-but-2-ynoylpyrrolidin-2-yl]imidazo[1,5-a]pyrazin-1-yl]-N-pyridin-2-ylbenzamide
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| Synonyms |
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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 |
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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) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.47 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (4.47 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (4.47 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 2% DMSO+30% PEG 300+2% Tween 80+ddH2O: 6mg/mL |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1482 mL | 10.7409 mL | 21.4818 mL | |
| 5 mM | 0.4296 mL | 2.1482 mL | 4.2964 mL | |
| 10 mM | 0.2148 mL | 1.0741 mL | 2.1482 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.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT04008706 | Active Recruiting |
Drug: Acalabrutinib | Chronic Lymphocytic Leukemia | AstraZeneca | September 17, 2019 | Phase 3 |
| NCT05256641 | Recruiting | Drug: Acalabrutinib | High-grade B-cell Lymphoma Transformed Lymphoma |
Jonsson Comprehensive Cancer Center |
January 23, 2023 | Phase 1 Phase 2 |
| NCT05951959 | Not yet recruiting | Drug: Acalabrutinib Drug: Venetoclax |
Mantle Cell Lymphoma (MCL) |
AstraZeneca | November 9, 2023 | Phase 2 |
| NCT05004064 | Not yet recruiting | Drug: Acalabrutinib Drug: Rituximab |
Mantle Cell Lymphoma | University College, London | January 1, 2023 | Phase 2 |
| NCT04402138 | Active Recruiting |
Drug: Acalabrutinib | Mantle Cell Lymphoma | SCRI Development Innovations, LLC |
August 7, 2020 | Phase 2 |
Acalabrutinib demonstrates equalin vitroon-target effects as ibrutinib.Clin Cancer Res.2017 Jun 1;23(11):2831-2841. |
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Acalabrutinib demonstrates on target effects and reduced proliferation and tumor burden in the CLL xenograft mouse model.Clin Cancer Res.2017 Jun 1;23(11):2831-2841. |
Acalabrutinib demonstrates significant and sustained inhibition of BCR signaling in the TCL1 adoptive transfer model.Clin Cancer Res.2017 Jun 1;23(11):2831-2841. |
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