Details of the Drug Combination

General Information of Drug Combination (ID: DC6UM7H)

• Drug Combination Name: Leuprolide + Bicalutamide
• Indication: Adenocarcinoma of the Prostate; Status: Phase 1 [1]
• Component Drugs:
  Leuprolide (DM5XPIJ): Small molecular drug
  Bicalutamide (DMZMSPF): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Leuprolide

Disease Entry	ICD 11	Status	REF
Plasma cell myeloma	2A83.1	Approved	[2]
Prostate cancer	2C82.0	Approved	[3]
Endometriosis	GA10	Investigative	[2]

Leuprolide Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Leutinizing-hormone-releasing hormone (GNRH1)	TT0ID4A	GON1_HUMAN	Activator	[6]

Leuprolide Interacts with 3 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Thyroxine-binding globulin (SERPINA7)	OTUYVTSU	THBG_HUMAN	Increases ADR	[7]
Thyroid peroxidase (TPO)	OTJJLL20	PERT_HUMAN	Increases ADR	[7]
Protein bric-a-brac 2 (bab2)	OTNNK0KI	BAB2_DROME	Increases ADR	[7]

Indication(s) of Bicalutamide

Disease Entry	ICD 11	Status	REF
Prostate cancer	2C82.0	Approved	[4]
Castration-resistant prostate carcinoma	N.A.	Investigative	[5]
Metastatic prostate carcinoma	N.A.	Investigative	[5]

Bicalutamide Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Androgen receptor (AR)	TTS64P2	ANDR_HUMAN	Antagonist	[13]

Bicalutamide Interacts with 2 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[14]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[14]

Bicalutamide Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[15]

Bicalutamide Interacts with 127 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Androgen receptor (AR)	OTUBKAZZ	ANDR_HUMAN	Decreases Response To Substance	[16]
Telomerase reverse transcriptase (TERT)	OT085VVA	TERT_HUMAN	Decreases Expression	[8]
Neuropilin-1 (NRP1)	OTCGULYV	NRP1_HUMAN	Decreases Expression	[8]
Calmegin (CLGN)	OTEWVFQV	CLGN_HUMAN	Increases Expression	[8]
Baculoviral IAP repeat-containing protein 5 (BIRC5)	OTILXZYL	BIRC5_HUMAN	Decreases Expression	[8]
Protein regulator of cytokinesis 1 (PRC1)	OTHD0XS0	PRC1_HUMAN	Decreases Expression	[8]
Mitotic checkpoint serine/threonine-protein kinase BUB1 beta (BUB1B)	OT8KME51	BUB1B_HUMAN	Decreases Expression	[8]
H/ACA ribonucleoprotein complex subunit DKC1 (DKC1)	OTX7DJR6	DKC1_HUMAN	Decreases Expression	[8]
Nebulette (NEBL)	OT2WH1NC	NEBL_HUMAN	Increases Expression	[8]
Kinesin-like protein KIF20A (KIF20A)	OTXOQHE0	KI20A_HUMAN	Decreases Expression	[8]
Anterior gradient protein 2 homolog (AGR2)	OTRRZT7W	AGR2_HUMAN	Increases Expression	[8]
Myc proto-oncogene protein (MYC)	OTPV5LUK	MYC_HUMAN	Decreases Expression	[8]
Pro-glucagon (GCG)	OTXU08VF	GLUC_HUMAN	Decreases Expression	[8]
Thymidine kinase, cytosolic (TK1)	OTY5JFM1	KITH_HUMAN	Decreases Expression	[8]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Increases Expression	[8]
Cholinesterase (BCHE)	OTOH3WQ9	CHLE_HUMAN	Decreases Expression	[8]
Cyclin-dependent kinase 1 (CDK1)	OTW1SC2N	CDK1_HUMAN	Decreases Expression	[8]
Prostate-specific antigen (KLK3)	OTFGSBFJ	KLK3_HUMAN	Decreases Expression	[8]
Amino acid transporter heavy chain SLC3A2 (SLC3A2)	OTBR33M9	4F2_HUMAN	Increases Expression	[8]
Interferon-induced protein with tetratricopeptide repeats 1 (IFIT1)	OTXOQDSG	IFIT1_HUMAN	Decreases Expression	[8]
Proliferating cell nuclear antigen (PCNA)	OTHZ1RIA	PCNA_HUMAN	Decreases Expression	[8]
Prostatic acid phosphatase (ACP3)	OTSIM0YG	PPAP_HUMAN	Decreases Expression	[8]
Cyclic AMP-dependent transcription factor ATF-3 (ATF3)	OTC1UOHP	ATF3_HUMAN	Increases Expression	[8]
C-X-C motif chemokine 3 (CXCL3)	OTSL94KH	CXCL3_HUMAN	Increases Expression	[8]
Kallikrein-2 (KLK2)	OT9RE37R	KLK2_HUMAN	Decreases Expression	[8]
Lamin-B1 (LMNB1)	OT100T3P	LMNB1_HUMAN	Decreases Expression	[8]
Midkine (MDK)	OTF24HKC	MK_HUMAN	Increases Expression	[8]
Growth arrest and DNA damage-inducible protein GADD45 alpha (GADD45A)	OTDRV63V	GA45A_HUMAN	Increases Expression	[8]
Protein S100-P (S100P)	OTJCXNJG	S100P_HUMAN	Increases Expression	[8]
Ribonucleoside-diphosphate reductase subunit M2 (RRM2)	OTOB6J6R	RIR2_HUMAN	Decreases Expression	[8]
Stress-induced-phosphoprotein 1 (STIP1)	OT7TXLOX	STIP1_HUMAN	Decreases Expression	[8]
Cyclin-dependent kinases regulatory subunit 2 (CKS2)	OTPTMHIV	CKS2_HUMAN	Decreases Expression	[8]
Mannosyl-oligosaccharide 1,2-alpha-mannosidase IA (MAN1A1)	OT6LIGJP	MA1A1_HUMAN	Increases Expression	[8]
Glypican-1 (GPC1)	OTQKRSSV	GPC1_HUMAN	Decreases Expression	[8]
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Increases Expression	[8]
Cyclin-dependent kinase 4 inhibitor C (CDKN2C)	OTCLOV90	CDN2C_HUMAN	Decreases Expression	[8]
Ran-specific GTPase-activating protein (RANBP1)	OTQE226K	RANG_HUMAN	Decreases Expression	[8]
Proliferation marker protein Ki-67 (MKI67)	OTA8N1QI	KI67_HUMAN	Decreases Expression	[8]
DNA replication licensing factor MCM2 (MCM2)	OTGGORIQ	MCM2_HUMAN	Decreases Expression	[8]
Aldehyde dehydrogenase family 3 member A2 (ALDH3A2)	OT714BUO	AL3A2_HUMAN	Increases Expression	[8]
Serine/threonine-protein kinase Nek2 (NEK2)	OT1H27HO	NEK2_HUMAN	Decreases Expression	[8]
Thyroxine 5-deiodinase (DIO3)	OTNTITOT	IOD3_HUMAN	Increases Expression	[8]
Neutrophil gelatinase-associated lipocalin (LCN2)	OTSB42BR	NGAL_HUMAN	Increases Expression	[8]
Cell division cycle protein 20 homolog (CDC20)	OTCOEZRV	CDC20_HUMAN	Decreases Expression	[8]
Mitotic spindle assembly checkpoint protein MAD2A (MAD2L1)	OTXNGZCG	MD2L1_HUMAN	Decreases Expression	[8]
Sequestosome-1 (SQSTM1)	OTGY5D5J	SQSTM_HUMAN	Increases Expression	[8]
Transmembrane glycoprotein NMB (GPNMB)	OTB7KQKV	GPNMB_HUMAN	Increases Expression	[8]
3-beta-hydroxysteroid-Delta(8),Delta(7)-isomerase (EBP)	OTSMGKXQ	EBP_HUMAN	Decreases Expression	[8]
Quinone oxidoreductase PIG3 (TP53I3)	OTSCM68G	QORX_HUMAN	Increases Expression	[8]
Retinoic acid-induced protein 3 (GPRC5A)	OTPOCWR7	RAI3_HUMAN	Decreases Expression	[8]
Fibroblast growth factor 13 (FGF13)	OTHNNVSG	FGF13_HUMAN	Increases Expression	[8]
Lymphokine-activated killer T-cell-originated protein kinase (PBK)	OT5Z27TW	TOPK_HUMAN	Decreases Expression	[8]
Tribbles homolog 3 (TRIB3)	OTG5OS7X	TRIB3_HUMAN	Increases Expression	[8]
BRCA1-associated RING domain protein 1 (BARD1)	OTTC0Z9Y	BARD1_HUMAN	Decreases Expression	[8]
Homeobox protein Nkx-3.1 (NKX3-1)	OT0DO6ZU	NKX31_HUMAN	Decreases Expression	[8]
GTP-binding protein 2 (GTPBP2)	OTOJ1KUA	GTPB2_HUMAN	Increases Expression	[8]
Nucleolar and spindle-associated protein 1 (NUSAP1)	OT85HIJ5	NUSAP_HUMAN	Decreases Expression	[8]
Peroxisomal trans-2-enoyl-CoA reductase (PECR)	OT5MS8EM	PECR_HUMAN	Increases Expression	[8]
Protein Niban 1 (NIBAN1)	OTYOLI12	NIBA1_HUMAN	Increases Expression	[8]
Rac GTPase-activating protein 1 (RACGAP1)	OTQE8IEH	RGAP1_HUMAN	Decreases Expression	[8]
E3 ubiquitin-protein ligase CCNB1IP1 (CCNB1IP1)	OTOTVMC8	CIP1_HUMAN	Increases Expression	[8]
Peptidyl-prolyl cis-trans isomerase FKBP11 (FKBP11)	OTY2GC67	FKB11_HUMAN	Increases Expression	[8]
DnaJ homolog subfamily B member 9 (DNAJB9)	OT38EQT6	DNJB9_HUMAN	Increases Expression	[8]
Alpha-methylacyl-CoA racemase (AMACR)	OTUU22PK	AMACR_HUMAN	Decreases Expression	[8]
E3 ISG15--protein ligase HERC5 (HERC5)	OTZ5PR39	HERC5_HUMAN	Increases Expression	[8]
Cell cycle progression protein 1 (CCPG1)	OT0IHDKL	CCPG1_HUMAN	Increases Expression	[8]
Targeting protein for Xklp2 (TPX2)	OTWLJYH0	TPX2_HUMAN	Decreases Expression	[8]
Cystine/glutamate transporter (SLC7A11)	OTKJ6PXW	XCT_HUMAN	Increases Expression	[8]
Lysosome-associated membrane glycoprotein 3 (LAMP3)	OTN0XL3W	LAMP3_HUMAN	Increases Expression	[8]
Hypoxia up-regulated protein 1 (HYOU1)	OTBGBSOV	HYOU1_HUMAN	Increases Expression	[8]
Electrogenic sodium bicarbonate cotransporter 1 (SLC4A4)	OT727K92	S4A4_HUMAN	Decreases Expression	[8]
Kunitz-type protease inhibitor 2 (SPINT2)	OTQV7BKQ	SPIT2_HUMAN	Increases Expression	[9]
Neprilysin (MME)	OT5Q39P8	NEP_HUMAN	Increases Expression	[9]
Retinoic acid receptor beta (RARB)	OT367U3E	RARB_HUMAN	Increases Expression	[9]
S-adenosylmethionine decarboxylase proenzyme (AMD1)	OTKAGZY3	DCAM_HUMAN	Increases Expression	[9]
CD9 antigen (CD9)	OT2184XU	CD9_HUMAN	Increases Expression	[9]
Long-chain-fatty-acid--CoA ligase 1 (ACSL1)	OTB06ESI	ACSL1_HUMAN	Increases Expression	[9]
Histone H2B type 1-B (H2BC3)	OT1BLFJO	H2B1B_HUMAN	Increases Expression	[9]
Lipopolysaccharide-responsive and beige-like anchor protein (LRBA)	OTOUZN9G	LRBA_HUMAN	Increases Expression	[9]
Synaptosomal-associated protein 25 (SNAP25)	OTUIQ81Q	SNP25_HUMAN	Increases Expression	[9]
Sorbitol dehydrogenase (SORD)	OTC44CR6	DHSO_HUMAN	Increases Expression	[9]
Rod outer segment membrane protein 1 (ROM1)	OTE7H0YV	ROM1_HUMAN	Increases Expression	[9]
BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3)	OT4SO7J4	BNIP3_HUMAN	Increases Expression	[9]
Cyclin-G2 (CCNG2)	OTII38K2	CCNG2_HUMAN	Increases Expression	[9]
Unconventional myosin-VI (MYO6)	OTJQYRC7	MYO6_HUMAN	Increases Expression	[9]
Retinoblastoma-associated protein (RB1)	OTQJUJMZ	RB_HUMAN	Increases Phosphorylation	[10]
Arginase-1 (ARG1)	OTHZITAM	ARGI1_HUMAN	Decreases Expression	[17]
Arginase-2, mitochondrial (ARG2)	OTCPI0E8	ARGI2_HUMAN	Increases Expression	[17]
Arf-GAP with SH3 domain, ANK repeat and PH domain-containing protein 2 (ASAP2)	OTGEXULW	ASAP2_HUMAN	Increases Expression	[11]
Bile salt export pump (ABCB11)	OTRU7THO	ABCBB_HUMAN	Decreases Activity	[18]
Low-density lipoprotein receptor (LDLR)	OTH559LU	LDLR_HUMAN	Affects Localization	[19]
Cytochrome P450 1A1 (CYP1A1)	OTE4EFH8	CP1A1_HUMAN	Decreases Activity	[20]
Insulin-like growth factor I (IGF1)	OTIIZR61	IGF1_HUMAN	Increases Expression	[21]
Beta-2 adrenergic receptor (ADRB2)	OTSDOX4Q	ADRB2_HUMAN	Decreases Expression	[22]
Beta-microseminoprotein (MSMB)	OTYORAJC	MSMB_HUMAN	Decreases Expression	[23]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Increases Expression	[24]
Prolactin-inducible protein (PIP)	OTH719AH	PIP_HUMAN	Decreases Expression	[25]
Cadherin-1 (CDH1)	OTFJMXPM	CADH1_HUMAN	Affects Localization	[19]
Lysosome-associated membrane glycoprotein 2 (LAMP2)	OTLUGEJC	LAMP2_HUMAN	Increases Expression	[11]
G2/mitotic-specific cyclin-B1 (CCNB1)	OT19S7E5	CCNB1_HUMAN	Decreases Expression	[26]
Insulin-like growth factor-binding protein 3 (IGFBP3)	OTIX63TX	IBP3_HUMAN	Decreases Expression	[21]
Insulin-like growth factor-binding protein 2 (IGFBP2)	OTG1P60E	IBP2_HUMAN	Increases Expression	[21]
Cyclin-A2 (CCNA2)	OTPHHYZJ	CCNA2_HUMAN	Decreases Expression	[26]
Phosphatidylcholine translocator ABCB4 (ABCB4)	OTE6PY83	MDR3_HUMAN	Decreases Activity	[18]
G1/S-specific cyclin-D1 (CCND1)	OT8HPTKJ	CCND1_HUMAN	Decreases Expression	[27]
Retinoic acid receptor RXR-beta (RXRB)	OTNPDXG2	RXRB_HUMAN	Decreases Expression	[24]
Coatomer subunit beta' (COPB2)	OT82JIGC	COPB2_HUMAN	Increases Expression	[11]
Cyclin-dependent kinase inhibitor 1B (CDKN1B)	OTNY5LLZ	CDN1B_HUMAN	Increases Expression	[24]
ATP synthase subunit e, mitochondrial (ATP5ME)	OTADVEE2	ATP5I_HUMAN	Increases Expression	[11]
Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN)	OTOWDUNT	PTEN_HUMAN	Increases Activity	[28]
26S proteasome complex subunit SEM1 (SEM1)	OTASLBM1	SEM1_HUMAN	Increases Expression	[11]
Thymosin beta-4 (TMSB4X)	OT9HPLP3	TYB4_HUMAN	Increases Expression	[29]
Apoptosis regulator BAX (BAX)	OTAW0V4V	BAX_HUMAN	Increases Expression	[27]
Bcl-2-like protein 1 (BCL2L1)	OTRC5K9O	B2CL1_HUMAN	Decreases Expression	[27]
Peptidyl-prolyl cis-trans isomerase FKBP5 (FKBP5)	OT404F9K	FKBP5_HUMAN	Decreases Expression	[27]
Angio-associated migratory cell protein (AAMP)	OTZXBSS4	AAMP_HUMAN	Increases Expression	[11]
Translocating chain-associated membrane protein 1 (TRAM1)	OT3I0H8E	TRAM1_HUMAN	Increases Expression	[11]
Cytochrome P450 1B1 (CYP1B1)	OTYXFLSD	CP1B1_HUMAN	Decreases Activity	[30]
Phosphatidate cytidylyltransferase, mitochondrial (TAMM41)	OTXBJ9W5	TAM41_HUMAN	Increases Expression	[11]
Cell division control protein 6 homolog (CDC6)	OTX93FE7	CDC6_HUMAN	Decreases Expression	[26]
Cytochrome c oxidase assembly factor 1 homolog (COA1)	OTHSX40F	COA1_HUMAN	Increases Expression	[11]
Ankyrin repeat and IBR domain-containing protein 1 (ANKIB1)	OTGKB7Y2	AKIB1_HUMAN	Increases Expression	[11]
Methyl-CpG-binding domain protein 2 (MBD2)	OTUQPP0R	MBD2_HUMAN	Increases Expression	[11]
Beta-1,4-galactosyltransferase 6 (B4GALT6)	OTBM8F2U	B4GT6_HUMAN	Increases Expression	[11]
BTB/POZ domain-containing protein 3 (BTBD3)	OTZ607YT	BTBD3_HUMAN	Increases Expression	[11]
Proliferation-associated protein 2G4 (PA2G4)	OT7IG7HT	PA2G4_HUMAN	Increases Response To Substance	[31]
Neurotensin/neuromedin N (NTS)	OTPGDNQS	NEUT_HUMAN	Decreases Response To Substance	[32]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Prostatic Neoplasms	DCWYSTW	N. A.	Phase 1	[33]

References

• [1] ClinicalTrials.gov (NCT02064036) Stereotactic Boost and Long-Term Androgen Deprivation for Adenocarcinoma of the Prostate
• [2] Leuprolide FDA Label
• [3] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 1175).
• [4] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 2863).
• [5] Bicalutamide FDA Label
• [6] Increased risk of metabolic syndrome, diabetes mellitus, and cardiovascular disease in men receiving androgen deprivation therapy for prostate cancer. Pharmacotherapy. 2008 Dec;28(12):1511-22.
• [7] ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
• [8] Microarray analysis of bicalutamide action on telomerase activity, p53 pathway and viability of prostate carcinoma cell lines. J Pharm Pharmacol. 2005 Jan;57(1):83-92.
• [9] Casodex treatment induces hypoxia-related gene expression in the LNCaP prostate cancer progression model. BMC Urol. 2005 Mar 24;5:5.
• [10] Therapeutic potential of CDK inhibitor NU2058 in androgen-independent prostate cancer. Oncogene. 2007 Dec 6;26(55):7611-9.
• [11] Differentially expressed genes in the prostate cancer cell line LNCaP after exposure to androgen and anti-androgen. Cancer Genet Cytogenet. 2006 Apr 15;166(2):130-8. doi: 10.1016/j.cancergencyto.2005.09.012.
• [12] Genome-wide impact of androgen receptor trapped clone-27 loss on androgen-regulated transcription in prostate cancer cells. Cancer Res. 2009 Apr 1;69(7):3140-7. doi: 10.1158/0008-5472.CAN-08-3738. Epub 2009 Mar 24.
• [13] Androgen receptor overexpression induces tamoxifen resistance in human breast cancer cells. Breast Cancer Res Treat. 2010 May;121(1):1-11.
• [14] Effects of the ABCG2 and ABCB1 drug transporter polymorphisms on the pharmacokinetics of bicalutamide in humans. Clin Chim Acta. 2015 Jan 1;438:7-11.
• [15] Bicalutamide: clinical pharmacokinetics and metabolism. Clin Pharmacokinet. 2004;43(13):855-78.
• [16] Possible role of adaptive mutation in resistance to antiandrogen in prostate cancer cells. Prostate. 2005 Nov 1;65(3):268-75. doi: 10.1002/pros.20282.
• [17] Androgen-regulated expression of arginase 1, arginase 2 and interleukin-8 in human prostate cancer. PLoS One. 2010 Aug 11;5(8):e12107.
• [18] Evaluating the Role of Multidrug Resistance Protein 3 (MDR3) Inhibition in Predicting Drug-Induced Liver Injury Using 125 Pharmaceuticals. Chem Res Toxicol. 2017 May 15;30(5):1219-1229. doi: 10.1021/acs.chemrestox.7b00048. Epub 2017 May 4.
• [19] Labeling and identification of LNCaP cell surface proteins: a pilot study. Prostate. 2007 Jun 15;67(9):943-54. doi: 10.1002/pros.20580.
• [20] Structure-based virtual screening of CYP1A1 inhibitors: towards rapid tier-one assessment of potential developmental toxicants. Arch Toxicol. 2021 Sep;95(9):3031-3048. doi: 10.1007/s00204-021-03111-2. Epub 2021 Jun 28.
• [21] DHT and testosterone, but not DHEA or E2, differentially modulate IGF-I, IGFBP-2, and IGFBP-3 in human prostatic stromal cells. Am J Physiol Endocrinol Metab. 2006 May;290(5):E952-60. doi: 10.1152/ajpendo.00451.2005. Epub 2005 Dec 20.
• [22] Hormonal regulation of beta2-adrenergic receptor level in prostate cancer. Prostate. 2008 Jul 1;68(10):1133-42. doi: 10.1002/pros.20778.
• [23] In silico and in vitro assessment of androgen receptor antagonists. Comput Biol Chem. 2021 Jun;92:107490. doi: 10.1016/j.compbiolchem.2021.107490. Epub 2021 Apr 23.
• [24] Androgen sensitivity related proteins in hormone-sensitive and hormone-insensitive prostate cancer cell lines treated by androgen antagonist bicalutamide. Neoplasma. 2001;48(5):419-24.
• [25] Regulation of GCDFP-15 expression in human mammary cancer cells. Int J Mol Med. 1999 Aug;4(2):135-40. doi: 10.3892/ijmm.4.2.135.
• [26] Androgen receptor regulates Cdc6 in synchronized LNCaP cells progressing from G1 to S phase. J Cell Physiol. 2005 Aug;204(2):381-7. doi: 10.1002/jcp.20422.
• [27] Niclosamide and Bicalutamide Combination Treatment Overcomes Enzalutamide- and Bicalutamide-Resistant Prostate Cancer. Mol Cancer Ther. 2017 Aug;16(8):1521-1530. doi: 10.1158/1535-7163.MCT-16-0912. Epub 2017 May 12.
• [28] Conditional expression of PTEN alters the androgen responsiveness of prostate cancer cells. Prostate. 2006 Jul 1;66(10):1114-23. doi: 10.1002/pros.20447.
• [29] Downregulation of thymosin beta4 expression by androgen in prostate cancer LNCaP cells. J Androl. 2008 Mar-Apr;29(2):207-12. doi: 10.2164/jandrol.107.003608. Epub 2007 Oct 3.
• [30] Association of CYP1A1 and CYP1B1 inhibition in in vitro assays with drug-induced liver injury. J Toxicol Sci. 2021;46(4):167-176. doi: 10.2131/jts.46.167.
• [31] The ErbB3-binding protein Ebp1 suppresses androgen receptor-mediated gene transcription and tumorigenesis of prostate cancer cells. Proc Natl Acad Sci U S A. 2005 Jul 12;102(28):9890-5. doi: 10.1073/pnas.0503829102. Epub 2005 Jun 30.
• [32] A role for neurotensin in bicalutamide resistant prostate cancer cells. Prostate. 2007 Feb 1;67(2):190-202. doi: 10.1002/pros.20518.
• [33] ClinicalTrials.gov (NCT00514917) A Study of Androgen Deprivation With Leuprolide, +/- Docetaxel for Clinically Asymptomatic Prostate Cancer Participants With a Rising Prostate Specific Antigen (PSA)