Table 3.

Drugs targeting intracrine enzymes.

	Inhibitor name (if known); (Drug Bank ID#)
	Developmental phase&			Approved drugs
Name	Discovery	Preclinical indication	Clinical indication	Inhibitor name	Indication
CYP11A1	✓	✓	✓	Aminoglutethimide (DB00357##)	Cushing's syndrome Breast cancer
CYP17A1	✓	✓	✓	Abiraterone (DB05812)	Prostate cancer, metastatic, castration-resistant
CYP19A1	✓	✓	Letrozole (DB01006)(19, 22, 24)	Anastrozole	Breast cancer: adjuvant treatment, metastatic
				(DB01217)
				Letrozole
				(DB01006)
				Exemestane	Breast cancer, palliative
				(DB00990)
				Formestane1
				Testolactone*
				(DB00894)
			Anastrozole (DB01217) (20, 23)
			Exemestane (DB00990) 21
			Advanced stage endometrial cancer, NSCLC∧, LAM∧∧
3βHSD1	✓	✓	✓	Trilostane* (DB01108)	Cushing's syndrome (veterinary use)
3βHSD2	✓	✓	✓	Trilostane* (DB01108)	Cushing's syndrome (veterinary use)
17βHSD1	✓	Endometriosis2,3
		Endometrial cancer4
		Breast cancer5,6
		Endometrial hyperplasia7
17βHSD2	8,9
17βHSD3&&		Prostate cancer10
17βHSD7	11
AKR1C1	12
AKR1C2	12
AKR1C3	✓	✓	ASP-952113 Prostate cancer**
			BAY 1128688 Endometriosis***
AKR1C4	12
SRD5A1	✓	✓	✓	Dutasteride (DB01126)	Prostatic hyperplasia (benign)
SRD5A2	✓	✓	✓	Finasteride (DB01216)	Prostatic hyperplasia (benign)
				Dutasteride (DB01126)
SRD5A3	✓	✓	✓	Dutasteride (DB01216)	Prostatic hyperplasia (benign)
STS	✓	✓	Irosustat (DB02292)
			Endometrial cancer 14,15
			Breast cancer14−17
			E2MATE/PLG2001
			Endometriosis18
SULT1E1	✓	✓	✓	Cyclizine (DB01176)	antistaminic for nausea/vomiting

^&‘Clinical phase’, i.e., in phase I, II or III trial; ‘Preclinical phase’ refers to in vivo testing; ‘Discovery phase’ any previous phase with some candidate compounds.

^#Drug Bank ID if the compound is deposited in Drug Bank database (www.drugbank.ca/drugs. Accessed on date: February 2018) (Wishart et al., 2018).

^##Aminoglutethimide (ID: DB00357) is an important inhibitor of CYP11A1 with inhibitory activity on CYP19A1 as well.

^*No longer on the market.

^&&17βHSD3 is testis specific and the reactions catalyzed by this enzyme are not reported in Figure 2.

^**This trial for prostate cancer was prematurely terminated (www.clinicaltrials.gov, NCT01352208).

^***Phase I trial is concluded (www.clinicaltrials.gov, NCT02434640. Accessed on date: February 2018) and a phase II trial started 2016 (http://adisinsight.springer.com/drugs/800041929).

^∧NSCLC: non-small cell lung cancer

^∧∧LAM: lymphangioleiomyomatosis

¹Perez Carrion et al. (1994), ²Arnold and Einspanier (2013), ³Delvoux et al. (2014), ⁴Konings et al. (2017), ⁵Järvensivu et al. (2018), ⁶Husen et al. (2006), ⁷Saloniemi et al. (2010), ⁸Gargano et al. (2015), ⁹Soubhye et al. (2015) ¹⁰Day et al. (2013), ¹¹ Wang et al. (2017), ¹²BroŽic et al. (2011), ¹³ Kikuchi et al. (2014), ¹⁴Purohit and Foster (2012), ¹⁵Pautier et al. (2017), ¹⁶Palmieri et al. (2017a), ¹⁷Palmieri et al. (2017b), ¹⁸Pohl et al. (2014), ¹⁹Ma et al. (2004), ²⁰Rose et al. (2000), ²¹Lindemann et al. (2014), ²²Slomovitz et al. (2015), ²³ NCT00932152; ²⁵Lu et al. (2017).