Details of the Drug

General Information of Drug (ID: DM7GCVW)

• Drug Name: Acalabrutinib
• Synonyms: Calquence; UNII-I42748ELQW; I42748ELQW; Acalabrutinib [INN]; Acalabrutinib [USAN:INN]; Calquence (TN); Acalabrutinib(ACP196); Acalabrutinib (ACP-196); GTPL8912; Acalabrutinib (JAN/USAN/INN); SCHEMBL14637368; EX-A881; WDENQIQQYWYTPO-IBGZPJMESA-N; KS-000006AT; KS-000006AD; s8116; BDBM50175583; AKOS030526094; ZINC208774715; DB11703; CS-5356; DS-3326

Indication

Disease Entry	ICD 11	Status	REF
leukaemia	2A60-2B33	Approved	[1]
Mantle cell lymphoma	2A85.5	Approved	[2]
Chronic lymphocytic leukaemia	2A82.0	Phase 3	[3]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 2	[4]

• Affected Organisms: Humans and other mammals
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 465.5
  Logarithm of the Partition Coefficient (xlogp); 3
  Rotatable Bond Count (rotbonds); 4
  Hydrogen Bond Donor Count (hbonddonor); 2
  Hydrogen Bond Acceptor Count (hbondacc); 6
• Chemical Identifiers:
  Formula: C26H23N7O2
  IUPAC Name: 4-[8-amino-3-[(2S)-1-but-2-ynoylpyrrolidin-2-yl]imidazo[1,5-a]pyrazin-1-yl]-N-pyridin-2-ylbenzamide
  Canonical SMILES: CC#CC(=O)N1CCC[C@H]1C2=NC(=C3N2C=CN=C3N)C4=CC=C(C=C4)C(=O)NC5=CC=CC=N5
  InChI: 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
  InChIKey: WDENQIQQYWYTPO-IBGZPJMESA-N
• Cross-matching ID:
  PubChem CID: 71226662
  CAS Number: 1420477-60-6
  UNII: I42748ELQW
  DrugBank ID: DB11703
  TTD ID: D09PQZ
  INTEDE ID: DR0031
  ACDINA ID: D00005
• Repurposed Drugs (RPD): Click to Jump to the Detailed RPD Information of This Drug

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Tyrosine-protein kinase BTK (ATK)	TTGM6VW	BTK_HUMAN	Inhibitor	[2]
HUMAN bruton tyrosine kinase (BTK)	TTOWPER	BTK_HUMAN	Inhibitor	[5]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Substrate	[6]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Substrate	[6]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
C-reactive protein (CRP)	OT0RFT8F	CRP_HUMAN	Gene/Protein Processing	[7]
Cytochrome P450 3A4 (CYP3A4)	OTQGYY83	CP3A4_HUMAN	Regulation of Drug Effects	[8]
Interleukin-6 (IL6)	OTUOSCCU	IL6_HUMAN	Gene/Protein Processing	[7]

Molecular Expression Atlas of This Drug

• The Studied Disease: leukaemia
• ICD Disease Classification: 2A60-2B33

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Tyrosine-protein kinase BTK (ATK)	DTT	BTK	3.54E-01	0.24	0.56
Cytochrome P450 3A5 (CYP3A5)	DME	CYP3A5	1.34E-01	-2.79E-01	-7.05E-01
Cytochrome P450 3A4 (CYP3A4)	DME	CYP3A4	9.81E-01	2.72E-01	6.95E-01

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Acalabrutinib (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Ivosidenib	DM8S6T7	Moderate	Increased metabolism of Acalabrutinib caused by Ivosidenib mediated induction of CYP450 enzyme.	Acute myeloid leukaemia [2A60]	[9]
Arn-509	DMT81LZ	Major	Increased metabolism of Acalabrutinib caused by Arn-509 mediated induction of CYP450 enzyme.	Acute myeloid leukaemia [2A60]	[9]
Troleandomycin	DMUZNIG	Major	Decreased metabolism of Acalabrutinib caused by Troleandomycin mediated inhibition of CYP450 enzyme.	Bacterial infection [1A00-1C4Z]	[9]
Pexidartinib	DMS2J0Z	Moderate	Increased metabolism of Acalabrutinib caused by Pexidartinib mediated induction of CYP450 enzyme.	Bone/articular cartilage neoplasm [2F7B]	[9]
Osilodrostat	DMIJC9X	Moderate	Decreased metabolism of Acalabrutinib caused by Osilodrostat mediated inhibition of CYP450 enzyme.	Cushing syndrome [5A70]	[9]
MK-8228	DMOB58Q	Major	Decreased metabolism of Acalabrutinib caused by MK-8228 mediated inhibition of CYP450 enzyme.	Cytomegaloviral disease [1D82]	[9]
Tazemetostat	DMWP1BH	Moderate	Increased metabolism of Acalabrutinib caused by Tazemetostat mediated induction of CYP450 enzyme.	Follicular lymphoma [2A80]	[9]
Avapritinib	DMK2GZX	Major	Increased risk of bleeding by the combination of Acalabrutinib and Avapritinib.	Gastrointestinal stromal tumour [2B5B]	[9]
Brigatinib	DM7W94S	Moderate	Increased metabolism of Acalabrutinib caused by Brigatinib mediated induction of CYP450 enzyme.	Lung cancer [2C25]	[9]
PF-06463922	DMKM7EW	Moderate	Increased metabolism of Acalabrutinib caused by PF-06463922 mediated induction of CYP450 enzyme.	Lung cancer [2C25]	[9]
Selpercatinib	DMZR15V	Moderate	Decreased metabolism of Acalabrutinib caused by Selpercatinib mediated inhibition of CYP450 enzyme.	Lung cancer [2C25]	[9]
IPI-145	DMWA24P	Major	Decreased metabolism of Acalabrutinib caused by IPI-145 mediated inhibition of CYP450 enzyme.	Mature B-cell leukaemia [2A82]	[9]
Arry-162	DM1P6FR	Major	Increased risk of bleeding by the combination of Acalabrutinib and Arry-162.	Melanoma [2C30]	[9]
LGX818	DMNQXV8	Major	Increased risk of bleeding by the combination of Acalabrutinib and LGX818.	Melanoma [2C30]	[9]
Siponimod	DM2R86O	Major	Additive immunosuppressive effects by the combination of Acalabrutinib and Siponimod.	Multiple sclerosis [8A40]	[10]
Ocrelizumab	DMEZ2KH	Moderate	Additive immunosuppressive effects by the combination of Acalabrutinib and Ocrelizumab.	Multiple sclerosis [8A40]	[11]
Ozanimod	DMT6AM2	Major	Additive immunosuppressive effects by the combination of Acalabrutinib and Ozanimod.	Multiple sclerosis [8A40]	[12]
Fedratinib	DM4ZBK6	Major	Decreased metabolism of Acalabrutinib caused by Fedratinib mediated inhibition of CYP450 enzyme.	Myeloproliferative neoplasm [2A20]	[9]
Entrectinib	DMMPTLH	Moderate	Decreased metabolism of Acalabrutinib caused by Entrectinib mediated inhibition of CYP450 enzyme.	Non-small cell lung cancer [2C25]	[9]
Rucaparib	DM9PVX8	Moderate	Decreased metabolism of Acalabrutinib caused by Rucaparib mediated inhibition of CYP450 enzyme.	Ovarian cancer [2C73]	[9]
Abametapir	DM2RX0I	Moderate	Decreased metabolism of Acalabrutinib caused by Abametapir mediated inhibition of CYP450 enzyme.	Pediculosis [1G00]	[13]
Lefamulin	DME6G97	Moderate	Decreased metabolism of Acalabrutinib caused by Lefamulin mediated inhibition of CYP450 enzyme.	Pneumonia [CA40]	[14]
Voxelotor	DMCS6M5	Major	Decreased metabolism of Acalabrutinib caused by Voxelotor mediated inhibition of CYP450 enzyme.	Sickle-cell disorder [3A51]	[9]
Telotristat ethyl	DMDIYFZ	Moderate	Increased metabolism of Acalabrutinib caused by Telotristat ethyl mediated induction of CYP450 enzyme.	Small intestine developmental anomaly [DA90]	[9]
Larotrectinib	DM26CQR	Moderate	Decreased metabolism of Acalabrutinib caused by Larotrectinib mediated inhibition of CYP450 enzyme.	Solid tumour/cancer [2A00-2F9Z]	[9]
LEE011	DMMX75K	Major	Decreased metabolism of Acalabrutinib caused by LEE011 mediated inhibition of CYP450 enzyme.	Solid tumour/cancer [2A00-2F9Z]	[9]
Elagolix	DMB2C0E	Moderate	Increased metabolism of Acalabrutinib caused by Elagolix mediated induction of CYP450 enzyme.	Uterine fibroid [2E86]	[9]
Betrixaban	DM2C4RF	Major	Increased risk of bleeding by the combination of Acalabrutinib and Betrixaban.	Venous thromboembolism [BD72]	[9]

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
FD&C blue no. 2	E00446	2723854	Colorant
Ferric hydroxide oxide yellow	E00539	23320441	Colorant
Magnesium stearate	E00208	11177	lubricant
Silicon dioxide	E00670	Not Available	Anticaking agent; Opacifying agent; Viscosity-controlling agent
Titanium dioxide	E00322	26042	Coating agent; Colorant; Opacifying agent

Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Acalabrutinib 100 mg capsule	100 mg	Oral Capsule	Oral

Jump to Detail Pharmaceutical Formulation Page of This Drug

References

• [1] FDA Approved Drug Products from FDA Official Website. 2019. Application Number: (NDA) 210259
• [2] 2017 FDA drug approvals.Nat Rev Drug Discov. 2018 Feb;17(2):81-85.
• [3] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [4] ClinicalTrials.gov (NCT04346199) Acalabrutinib Study With Best Supportive Care Versus Best Supportive Care in Subjects Hospitalized With COVID-19.. U.S. National Institutes of Health.
• [5] AstraZeneca initiates CALAVI clinical trial with Calquence against COVID-19
• [6] FDA label of Acalabrutinib. The 2020 official website of the U.S. Food and Drug Administration.
• [7] Inhibition of Bruton tyrosine kinase in patients with severe COVID-19. Sci Immunol. 2020 Jun 5;5(48):eabd0110. doi: 10.1126/sciimmunol.abd0110. Epub 2020 Jun 5.
• [8] Functional assessment of the effects of CYP3A4 variants on acalabrutinib metabolism in vitro. Chem Biol Interact. 2021 Aug 25;345:109559. doi: 10.1016/j.cbi.2021.109559. Epub 2021 Jun 18.
• [9] Product Information. Calquence (acalabrutinib). Astra-Zeneca Pharmaceuticals, Wilmington, DE.
• [10] Cerner Multum, Inc. "Australian Product Information.".
• [11] Product Information. Ocrevus (ocrelizumab). Genentech, South San Francisco, CA.
• [12] Cerner Multum, Inc. "UK Summary of Product Characteristics.".
• [13] Product Information. Xeglyze (abametapir topical). Dr. Reddy's Laboratories Inc, Upper Saddle River, NJ.
• [14] Product Information. Xenleta (lefamulin). Nabriva Therapeutics US, Inc., King of Prussia, PA.