Details of the Drug-Related molecule(s) Interaction Atlas

General Information of DTT (ID: TTGM6VW)

• DTT Name: Tyrosine-protein kinase BTK (ATK) DTT Info
• Gene Name: BTK

Molecule-Related Drug & Molecule List

4 Approved Drug(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Acalabrutinib	DM7GCVW	leukaemia	2A60-2B33	Approved	[1]
Ibrutinib	DMHZCPO	Mantle cell lymphoma	2A85.5	Approved	[2]
Pirtobrutinib	DMRG1X3	Non-hodgkin lymphoma	2B33.5	Approved	[3]
Zanubrutinib	DMJWRQP	Mantle cell lymphoma	2A85.5	Approved	[4]

34 Clinical Trial Drug(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
GDC-0853	DMBEL3Q	Multiple sclerosis	8A40	Phase 3	[5]
ICP-022	DMU72KL	Chronic lymphocytic leukaemia	2A82.0	Phase 3	[6]
Tolebrutinib	DML19V6	Multiple sclerosis	8A40	Phase 3	[7]
ARQ 531	DMRG0A3	Hematologic tumour	2B33.Y	Phase 2	[8]
BGB-3112	DMQCFSM	Follicular lymphoma	2A80	Phase 2	[8]
BMS-986142	DMZB8AJ	Rheumatoid arthritis	FA20	Phase 2	[5]
Branebrutinib	DM97I5L	Rheumatoid arthritis	FA20	Phase 2	[9]
CC-292	DMJR9H0	Chronic lymphocytic leukaemia	2A82.0	Phase 2	[10]
DTRM-555	DMX27IT	Chronic lymphocytic leukaemia	2A82.0	Phase 2	[11]
GS-4059	DMHQV6R	B-cell lymphoma	2A86	Phase 2	[8]
LOU064	DME8O5K	Chronic idiopathic urticaria	EB00.1	Phase 2	[12]
M2951	DMC5MQD	Multiple sclerosis	8A40	Phase 2	[5]
PRN1008	DMBZ6CP	Pemphigus vulgaris	EB40	Phase 2	[5]
SAR 444727	DMWPMN2	Atopic dermatitis	EA80	Phase 2	[13]
ACP-319	DM7IWTF	Chronic lymphocytic leukaemia	2A82.0	Phase 1/2	[2]
CG-806	DMPYW28	Acute myeloid leukaemia	2A60	Phase 1/2	[14]
Vecabrutinib	DM8A5E0	B-cell lymphoma	2A86	Phase 1/2	[8]
AC0058TA	DMB5A63	Autoimmune disease	4A40-4A45	Phase 1	[5]
BGB-16673	DM7X6IB	B-cell lymphoma	2A86	Phase 1	[15]
BGB-3113	DMIF9DZ	B-cell lymphoma	2A86	Phase 1	[8]
BIIB068	DMVS87W	Systemic lupus erythematosus	4A40.0	Phase 1	[5]
BIIB091	DMW49ZF	Multiple sclerosis	8A40	Phase 1	[16]
DTRMWXHS-12	DM5AGKV	B-cell lymphoma	2A86	Phase 1	[17]
HM71224	DME4D7H	Rheumatoid arthritis	FA20	Phase 1	[18]
HMPL-760	DMHC5YG	Chronic lymphocytic leukaemia	2A82.0	Phase 1	[19]
JNJ-64264681	DMLYAGD	Chronic lymphocytic leukaemia	2A82.0	Phase 1	[20]
M7583	DMDK4MG	Haematological malignancy	2B33.Y	Phase 1	[8]
NX-2127	DMIE2OG	Chronic lymphocytic leukaemia	2A82.0	Phase 1	[21]
NX-5948	DM6GHMC	Chronic lymphocytic leukaemia	2A82.0	Phase 1	[21]
ONO-4059	DMC29LV	B-cell lymphoma	2A86	Phase 1	[22]
PRN2246	DMQNS51	Multiple sclerosis	8A40	Phase 1	[23]
TAK-020	DM6OKH4	Rheumatoid arthritis	FA20	Phase 1	[5]
TG-1701	DMNDHKL	Chronic lymphocytic leukaemia	2A82.0	Phase 1	[24]
TT-01488	DMHTGB5	B-cell non-hodgkin lymphoma	2B33.5	Phase 1	[25]

26 Patented Agent(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Imidazopyridine derivative 4	DMP2AXV	N. A.	N. A.	Patented	[26]
PMID27774824-Compound-Figure12Example1	DMAGKNJ	N. A.	N. A.	Patented	[26]
PMID27774824-Compound-Figure12Example10	DMYOSIA	N. A.	N. A.	Patented	[26]
PMID27774824-Compound-Figure12Example61	DMNIZD7	N. A.	N. A.	Patented	[26]
Pyrazolo[4,3-c]pyridine derivative 2	DMCDFLQ	N. A.	N. A.	Patented	[26]
Pyrrolo[2,3-d]pyrimidine derivative 12	DMYTV49	N. A.	N. A.	Patented	[27]
Pyrrolo[2,3-d]pyrimidine derivative 13	DMTGELI	N. A.	N. A.	Patented	[27]
Pyrrolo[2,3-d]pyrimidine derivative 14	DMK4LOH	N. A.	N. A.	Patented	[27]
Pyrrolo[2,3-d]pyrimidine derivative 15	DMZ4PLC	N. A.	N. A.	Patented	[27]
Pyrrolo[2,3-d]pyrimidine derivative 16	DM1GYZQ	Autoimmune disease	4A40-4A45	Patented	[27]
Pyrrolo[2,3-d]pyrimidine derivative 17	DMXWVN2	Autoimmune disease	4A40-4A45	Patented	[27]
Pyrrolo[2,3-d]pyrimidine derivative 18	DMSXH8K	N. A.	N. A.	Patented	[27]
Pyrrolo[2,3-d]pyrimidine derivative 19	DMC9TGM	N. A.	N. A.	Patented	[27]
Pyrrolo[2,3-d]pyrimidine derivative 20	DM2E7DJ	N. A.	N. A.	Patented	[27]
Pyrrolo[2,3-d]pyrimidine derivative 21	DM9S07A	N. A.	N. A.	Patented	[27]
Pyrrolo[2,3-d]pyrimidine derivative 22	DMHWNSD	N. A.	N. A.	Patented	[27]
Pyrrolo[2,3-d]pyrimidine derivative 23	DMTMWKX	N. A.	N. A.	Patented	[27]
Pyrrolo[2,3-d]pyrimidine derivative 25	DMWU3O4	N. A.	N. A.	Patented	[27]
Pyrrolo[2,3-d]pyrimidine derivative 26	DMX1ANB	N. A.	N. A.	Patented	[27]
Pyrrolo[2,3-d]pyrimidine derivative 27	DMCZJ1W	N. A.	N. A.	Patented	[27]
Pyrrolo[2,3-d]pyrimidine derivative 28	DMXRJI2	N. A.	N. A.	Patented	[27]
Pyrrolo[2,3-d]pyrimidine derivative 29	DM6IJRG	N. A.	N. A.	Patented	[27]
Pyrrolo[2,3-d]pyrimidine derivative 30	DM57W29	N. A.	N. A.	Patented	[27]
Pyrrolo[2,3-d]pyrimidine derivative 31	DMA9PM4	N. A.	N. A.	Patented	[27]
Pyrrolo[2,3-d]pyrimidine derivative 32	DMQGI0R	N. A.	N. A.	Patented	[27]
Pyrrolo[2,3-d]pyrimidine derivative 33	DM6BTMX	N. A.	N. A.	Patented	[27]

1 Preclinical Drug(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PCI-45292	DMW3TGI	Autoimmune diabetes	5A10	Preclinical	[28]

1 Discontinued Drug(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
GDC-0834	DMOAURL	Rheumatoid arthritis	FA20	Terminated	[29]

7 Investigative Drug(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
CGI-1316	DMTPRBX	Autoimmune diabetes	5A10	Investigative	[2]
Inositol 1,3,4,5-Tetrakisphosphate	DMIFD35	Discovery agent	N.A.	Investigative	[30]
LFM-A13	DMTXWCZ	Discovery agent	N.A.	Investigative	[31]
PMID24900538C2c	DM5PATM	Discovery agent	N.A.	Investigative	[32]
PMID24915291C31	DMN7QB8	Discovery agent	N.A.	Investigative	[33]
PMID24915291C38	DMBXT9J	Discovery agent	N.A.	Investigative	[33]
RN486	DML7SQH	Discovery agent	N.A.	Investigative	[34]

References

• [1] 2017 FDA drug approvals.Nat Rev Drug Discov. 2018 Feb;17(2):81-85.
• [2] 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. (Target id: 1948).
• [3] Targeting BTK in CLL: Beyond Ibrutinib. Curr Hematol Malig Rep. 2019 Jun;14(3):197-205.
• [4] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
• [5] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [6] Clinical pipeline report, company report or official report of InnoCare Pharma.
• [7] Safety and efficacy of tolebrutinib, an oral brain-penetrant BTK inhibitor, in relapsing multiple sclerosis: a phase 2b, randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2021 Sep;20(9):729-738.
• [8] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [9] Safety, pharmacokinetics and pharmacodynamics of branebrutinib (BMS-986195), a covalent, irreversible inhibitor of Bruton's tyrosine kinase: Randomised phase I, placebo-controlled trial in healthy participants. Br J Clin Pharmacol. 2020 Sep;86(9):1849-1859.
• [10] Inhibition of Btk with CC-292 provides early pharmacodynamic assessment of activity in mice and humans. J Pharmacol Exp Ther. 2013 Aug;346(2):219-28.
• [11] ClinicalTrials.gov (NCT04305444) Study of a Triple Combination Therapy, DTRM-555, in Patients With R/R CLL or R/R Non-Hodgkin's Lymphomas. U.S. National Institutes of Health.
• [12] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [13] Preclinical Mechanisms of Topical PRN473, a Bruton Tyrosine Kinase Inhibitor, in Immune-Mediated Skin Disease Models. Immunohorizons. 2021 Jul 29;5(7):581-589.
• [14] Clinical pipeline report, company report or official report of Aptose Biosciences.
• [15] ClinicalTrials.gov (NCT05294731) A Phase 1, Open-Label, Dose-Escalation and Expansion Study of the Bruton Tyrosine Kinase Targeted Protein-Degrader BGB-16673 in Chinese Patients With B-Cell Malignancies. U.S.National Institutes of Health.
• [16] Discovery and Preclinical Characterization of BIIB091, a Reversible, Selective BTK Inhibitor for the Treatment of Multiple Sclerosis. J Med Chem. 2022 Jan 27;65(2):1206-1224.
• [17] ClinicalTrials.gov (NCT02900716) Safety Study of BTK Inhibitor, DTRMWXHS-12, Used Singly or in Combination, in CLL and B-cell Lymphomas. U.S. National Institutes of Health.
• [18] HM71224, a selective Bruton's tyrosine kinase inhibitor, attenuates the development of murine lupus. Arthritis Res Ther. 2017 Sep 26;19(1):211.
• [19] ClinicalTrials.gov (NCT05176691) A Multicenter, Open-label, Phase 1 Study Evaluating the Safety and Tolerability of HMPL-760 in Patients With Previously Treated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) or Other Non-Hodgkin Lymphoma (NHL). U.S.National Institutes of Health.
• [20] A Study of JNJ-64264681 and JNJ-67856633 in Participants With Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia
• [21] The Evolution of Therapies Targeting Bruton Tyrosine Kinase for the Treatment of Chronic Lymphocytic Leukaemia: Future Perspectives. Cancers (Basel). 2023 May 3;15(9):2596.
• [22] ONO-4059, a novel oral Bruton's tyrosine kinase (Btk) inhibitor that demonstrates potent pharmacodynamic activity through Phosphorylated Btk (P-Btk) inhibition, in addition to effective anti-tumour activity in a TMD-8 (DLBCL) xenograft model. Cancer Research. 08/2013; 73(8 Supplement):2452-2452.
• [23] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [24] Clinical pipeline report, company report or official report of TG Therapeutics.
• [25] ClinicalTrials.gov (NCT05683717) A Phase I, Multicenter, Open Label, and Dose-Escalation Study of TT-01488, Administered Orally in Adult Patients With B-Cell Malignancies. U.S.National Institutes of Health.
• [26] Inhibitors of JAK-family kinases: an update on the patent literature 2013-2015, part 1.Expert Opin Ther Pat. 2017 Feb;27(2):127-143.
• [27] Pyrrolo[2,3-d]pyrimidines active as Btk inhibitors.Expert Opin Ther Pat. 2017 Dec;27(12):1305-1318.
• [28] Ibrutinib is an irreversible molecular inhibitor of ITK driving a Th1-selective pressure in T lymphocytes. Blood. 2013 October 10; 122(15): 2539-2549.
• [29] Antiarthritis effect of a novel Bruton's tyrosine kinase (BTK) inhibitor in rat collagen-induced arthritis and mechanism-based pharmacokinetic/pharmacodynamic modeling: relationships between inhibition of BTK phosphorylation and efficacy. J Pharmacol Exp Ther. 2011 Jul;338(1):154-63.
• [30] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [31] A systematic interaction map of validated kinase inhibitors with Ser/Thr kinases. Proc Natl Acad Sci U S A. 2007 Dec 18;104(51):20523-8.
• [32] Discovery of Disubstituted Imidazo[4,5-b]pyridines and Purines as Potent TrkA Inhibitors. ACS Med Chem Lett. 2012 Jul 26;3(9):705-9.
• [33] Discovery of a series of 2,5-diaminopyrimidine covalent irreversible inhibitors of Bruton's tyrosine kinase with in vivo antitumor activity. J Med Chem. 2014 Jun 26;57(12):5112-28.
• [34] RN486, a selective Bruton's tyrosine kinase inhibitor, abrogates immune hypersensitivity responses and arthritis in rodents. J Pharmacol Exp Ther. 2012 Apr;341(1):90-103.