Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTNE1C7)

• DTT Name: Cytochrome P450 2J2
• Synonyms: Albendazole monooxygenase (hydroxylating); Albendazole monooxygenase (sulfoxide-forming); Arachidonic acid epoxygenase; CYPIIJ2; Hydroperoxy icosatetraenoate isomerase
• Gene Name: CYP2J2
• BioChemical Class: Single Protein
• UniProt ID: CP2J2_HUMAN
• TTD ID: TE0030
• Sequence:
  MLAAMGSLAAALWAVVHPRTLLLGTVAFLLAADFLKRRRPKNYPPGPWRLPFLGNFFLVD
  FEQSHLEVQLFVKKYGNLFSLELGDISAVLITGLPLIKEALIHMDQNFGNRPVTPMREHI
  FKKNGLIMSSGQAWKEQRRFTLTALRNFGLGKKSLEERIQEEAQHLTEAIKEENGQPFDP
  HFKINNAVSNIICSITFGERFEYQDSWFQQLLKLLDEVTYLEASKTCQLYNVFPWIMKFL
  PGPHQTLFSNWKKLKLFVSHMIDKHRKDWNPAETRDFIDAYLKEMSKHTGNPTSSFHEEN
  LICSTLDLFFAGTETTSTTLRWALLYMALYPEIQEKVQAEIDRVIGQGQQPSTAARESMP
  YTNAVIHEVQRMGNIIPLNVPREVTVDTTLAGYHLPKGTMILTNLTALHRDPTEWATPDT
  FNPDHFLENGQFKKREAFMPFSIGKRACLGEQLARTELFIFFTSLMQKFTFRPPNNEKLS
  LKFRMGITISPVSHRLCAVPQV
• Function: A cytochrome P450 monooxygenase involved in the metabolism of polyunsaturated fatty acids (PUFA) in the cardiovascular system. Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the epoxidation of double bonds of PUFA. Converts arachidonic acid to four regioisomeric epoxyeicosatrienoic acids (EpETrE).

The Drug-Metabolizing Enzyme (DME) Role of This DTT

• DTT DME Name: Cytochrome P450 2J2 (CYP2J2) DME Info
• Gene Name: CYP2J2

8 Approved Drug(s) Metabolized by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Ergocalciferol	DMHO0AR	Hypoparathyroidism	5A50	Approved	[1]
Levomilnacipran	DMV26S8	Fibromyalgia	MG30.01	Approved	[]
Riociguat	DMXBLMP	Chronic thromboembolic pulmonary hypertension		Approved	[2]
Rivaroxaban	DMQMBZ1	Deep vein thrombosis	BD71	Approved	[3]
Vitamin D	DMWQUC9	N. A.	N. A.	Approved	[1]
Vorapaxar	DMA16BR	Myocardial infarction	BA41-BA43	Approved	[4]
Alfacalcidol	DM1237M	Hyperparathyroidism	5A51	Phase 4	[1]
Ebastine	DMH21D9	N. A.	N. A.	Phase 4	[5]

4 Clinical Trial Drug(s) Metabolized by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Carebastine	DMUVMWZ	Ocular allergy	4A81	Phase 3	[6]
Eperisone	DM1SMAI	Muscle spasm	MB47.3	Phase 3	[7]
MANIDIPINE	DMJPGUA	N. A.	N. A.	Phase 3	[8]
H3B-6545	DMIFCY2	Breast cancer	2C60-2C65	Phase 1/2	[9]

1 Discontinued Drug(s) Metabolized by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Astemizole	DM2HN6Q	Allergic rhinitis	CA08.0	Withdrawn from market	[5]

1 Investigative Drug(s) Metabolized by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Desmethylastemizole	DM58XJN	Discovery agent	N.A.	Investigative	[10]

References

• [1] Characterization of rat and human CYP2J enzymes as Vitamin D 25-hydroxylases. Steroids. 2006 Oct;71(10):849-56.
• [2] Riociguat (adempas): a novel agent for the treatment of pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension. P T. 2014 Nov;39(11):749-58.
• [3] Comparative efficacy and safety of the novel oral anticoagulants dabigatran, rivaroxaban and apixaban in preclinical and clinical development. Thromb Haemost. 2010 Mar;103(3):572-85.
• [4] Vorapaxar: the missing link in antiplatelet therapy! J Anaesthesiol Clin Pharmacol. 2017 Apr-Jun;33(2):269-270.
• [5] Identifying a selective substrate and inhibitor pair for the evaluation of CYP2J2 activity. Drug Metab Dispos. 2012 May;40(5):943-51.
• [6] Characterization of ebastine, hydroxyebastine, and carebastine metabolism by human liver microsomes and expressed cytochrome P450 enzymes: major roles for CYP2J2 and CYP3A. Drug Metab Dispos. 2006 Nov;34(11):1793-7.
• [7] Characterization of human cytochrome P450 enzymes involved in the biotransformation of eperisone. Xenobiotica. 2009 Jan;39(1):1-10.
• [8] Inhibitory effects of antihypertensive drugs on human cytochrome P450 2J2 activity: Potent inhibition by azelnidipine and manidipine. Chem Biol Interact. 2019 Jun 1;306:1-9.
• [9] Nonclinical pharmacokinetics and in vitro metabolism of H3B-6545, a novel selective ERalpha covalent antagonist (SERCA). Cancer Chemother Pharmacol. 2019 Jan;83(1):151-160.
• [10] Involvement of CYP2J2 on the intestinal first-pass metabolism of antihistamine drug, astemizole. Drug Metab Dispos. 2002 Nov;30(11):1240-5.