ABBV-744 | CAS#2138861-99-9 | BET bromodomain inhibitor

MedKoo Cat#: 206981 | Name: ABBV-744

Description:

WARNING: This product is for research use only, not for human or veterinary use.

ABBV-744 is a BDII-selective BET bromodomain inhibitor that is being investigated to treat AML and metastic castration-resistant prostate cancer. It halso has a strong affinity and stably complexes with the main protease (Mpro) enzyme of SARS-CoV-2

Chemical Structure

ABBV-744

CAS#2138861-99-9

Theoretical Analysis

MedKoo Cat#: 206981

Name: ABBV-744

CAS#: 2138861-99-9

Chemical Formula: C28H30FN3O4

Exact Mass: 491.2220

Molecular Weight: 491.56

Elemental Analysis: C, 68.42; H, 6.15; F, 3.86; N, 8.55; O, 13.02

Price and Availability

Size	Price	Availability
10mg	USD 150.00	Ready to ship
25mg	USD 300.00	Ready to ship
50mg	USD 550.00	Ready to ship
100mg	USD 950.00	Ready to ship
200mg	USD 1,450.00	Ready to ship
500mg	USD 2,650.00	Ready to ship
1g	USD 3,850.00	Ready to ship
2g	USD 6,450.00	2 Weeks

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Related CAS #

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Synonym

ABBV-744; ABBV 744; ABBV744.

IUPAC/Chemical Name

N-ethyl-4-(2-(4-fluoro-2,6-dimethylphenoxy)-5-(2-hydroxypropan-2-yl)phenyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxamide

InChi Key

OEDSFMUSNZDJFD-UHFFFAOYSA-N

InChi Code

InChI=1S/C28H30FN3O4/c1-7-30-26(33)22-13-20-21(14-32(6)27(34)24(20)31-22)19-12-17(28(4,5)35)8-9-23(19)36-25-15(2)10-18(29)11-16(25)3/h8-14,31,35H,7H2,1-6H3,(H,30,33)

SMILES Code

O=C(C(N1)=CC(C(C2=CC(C(C)(O)C)=CC=C2OC3=C(C)C=C(F)C=C3C)=CN4C)=C1C4=O)NCC

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#C9R01B21

QC Data

View QC data: current batch, Lot#C9R01B21

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

ABBV-744 is a highly BDII-selective BET bromodomain inhibitor.

In vitro activity:

Compound 46 (ABBV744) was tested for binding against the first and second bromodomains of BRD2, BRD3, and BRDt in the TR-FRET binding assay and displayed similarly potent and selective binding to that observed with BRD4 (Table 9). Whereas potent dual-bromodomain BET inhibitors such as 5 show potent antiproliferative effects against a wide range of cancer cell lines,46 shows substantially higher relative potency against cell lines derived from prostate cancer and AML, implying that BD1 inhibition is not required to inhibit proliferation in a subset of cancer indications. Reference: J Med Chem. 2020 May 28;63(10):5585-5623. https://pubmed.ncbi.nlm.nih.gov/32324999/

In vivo activity:

In a mouse xenograft model using LNCaP cells, treatment with 4.7 mg kg−1 ABBV-744 (1/16 of the maximum tolerated dose (MTD)) caused a delay in tumour growth that was equivalent to ABBV-075 treatment at the MTD dose of 1 mg kg−1 (Fig. 4a). Comparing efficacious exposure levels of ABBV-744 in LNCaP tumour-bearing mice (4.7 mg kg−1; area under the curve, 1.1 μg h ml−1) and MTD (75 mg kg−1; area under the curve, 13.1 μg h ml−1) demonstrated that ABBV-744 was able to produce significant antitumour activity at 1/12 of the highest tolerable exposure of ABBV-744 (Extended Data Fig. 8a). The activity exhibited by ABBV-744 at 1/16 of the MTD of ABBV-744 was superior to the activities achieved using JQ1 and iBET at their respective MTDs or, in the case of RVX-208, at the highest feasible dose in this model (Extended Data Fig. 8b, c). Similarly, ABBV-744 at 1/16 MTD also displayed equivalent or better antitumour activity compared with ABBV-075 at MTD in the enzalutamide-resistant MDA-PCa-2b xenograft model (Fig. 4b). Reference: Nature. 2020 Feb;578(7794):306-310. https://pubmed.ncbi.nlm.nih.gov/31969702/

	Solvent	mg/mL	mM
Solubility
	DMSO	33.6	68.29
	DMSO:PBS (pH 7.2) (1:3)	0.3	0.51
	DMF	30.0	61.03

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 491.56 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Fakhar Z, Khan S, AlOmar SY, Alkhuriji A, Ahmad A. ABBV-744 as a potential inhibitor of SARS-CoV-2 main protease enzyme against COVID-19. Sci Rep. 2021 Jan 8;11(1):234. doi: 10.1038/s41598-020-79918-3. PMID: 33420186; PMCID: PMC7794216. 2. Sheppard GS, Wang L, Fidanze SD, Hasvold LA, Liu D, Pratt JK, Park CH, Longenecker K, Qiu W, Torrent M, Kovar PJ, Bui M, Faivre E, Huang X, Lin X, Wilcox D, Zhang L, Shen Y, Albert DH, Magoc TJ, Rajaraman G, Kati WM, McDaniel KF. Discovery of N-Ethyl-4-[2-(4-fluoro-2,6-dimethyl-phenoxy)-5-(1-hydroxy-1-methyl-ethyl)phenyl]-6-methyl-7-oxo-1H-pyrrolo[2,3-c]pyridine-2-carboxamide (ABBV-744), a BET Bromodomain Inhibitor with Selectivity for the Second Bromodomain. J Med Chem. 2020 May 28;63(10):5585-5623. doi: 10.1021/acs.jmedchem.0c00628. Epub 2020 May 7. PMID: 32324999. 3. Sheppard GS, Wang L, Fidanze SD, Hasvold LA, Liu D, Pratt JK, Park CH, Longenecker K, Qiu W, Torrent M, Kovar PJ, Bui M, Faivre E, Huang X, Lin X, Wilcox D, Zhang L, Shen Y, Albert DH, Magoc TJ, Rajaraman G, Kati WM, McDaniel KF. Discovery of N-Ethyl-4-[2-(4-fluoro-2,6-dimethyl-phenoxy)-5-(1-hydroxy-1-methyl-ethyl)phenyl]-6-methyl-7-oxo-1H-pyrrolo[2,3-c]pyridine-2-carboxamide (ABBV-744), a BET Bromodomain Inhibitor with Selectivity for the Second Bromodomain. J Med Chem. 2020 May 28;63(10):5585-5623. doi: 10.1021/acs.jmedchem.0c00628. Epub 2020 May 7. PMID: 32324999. 4. Faivre EJ, McDaniel KF, Albert DH, Mantena SR, Plotnik JP, Wilcox D, Zhang L, Bui MH, Sheppard GS, Wang L, Sehgal V, Lin X, Huang X, Lu X, Uziel T, Hessler P, Lam LT, Bellin RJ, Mehta G, Fidanze S, Pratt JK, Liu D, Hasvold LA, Sun C, Panchal SC, Nicolette JJ, Fossey SL, Park CH, Longenecker K, Bigelow L, Torrent M, Rosenberg SH, Kati WM, Shen Y. Selective inhibition of the BD2 bromodomain of BET proteins in prostate cancer. Nature. 2020 Feb;578(7794):306-310. doi: 10.1038/s41586-020-1930-8. Epub 2020 Jan 22. PMID: 31969702.

In vitro protocol:

In vivo protocol:

1. Sheppard GS, Wang L, Fidanze SD, Hasvold LA, Liu D, Pratt JK, Park CH, Longenecker K, Qiu W, Torrent M, Kovar PJ, Bui M, Faivre E, Huang X, Lin X, Wilcox D, Zhang L, Shen Y, Albert DH, Magoc TJ, Rajaraman G, Kati WM, McDaniel KF. Discovery of N-Ethyl-4-[2-(4-fluoro-2,6-dimethyl-phenoxy)-5-(1-hydroxy-1-methyl-ethyl)phenyl]-6-methyl-7-oxo-1H-pyrrolo[2,3-c]pyridine-2-carboxamide (ABBV-744), a BET Bromodomain Inhibitor with Selectivity for the Second Bromodomain. J Med Chem. 2020 May 28;63(10):5585-5623. doi: 10.1021/acs.jmedchem.0c00628. Epub 2020 May 7. PMID: 32324999. 2. Faivre EJ, McDaniel KF, Albert DH, Mantena SR, Plotnik JP, Wilcox D, Zhang L, Bui MH, Sheppard GS, Wang L, Sehgal V, Lin X, Huang X, Lu X, Uziel T, Hessler P, Lam LT, Bellin RJ, Mehta G, Fidanze S, Pratt JK, Liu D, Hasvold LA, Sun C, Panchal SC, Nicolette JJ, Fossey SL, Park CH, Longenecker K, Bigelow L, Torrent M, Rosenberg SH, Kati WM, Shen Y. Selective inhibition of the BD2 bromodomain of BET proteins in prostate cancer. Nature. 2020 Feb;578(7794):306-310. doi: 10.1038/s41586-020-1930-8. Epub 2020 Jan 22. PMID: 31969702.

1: Faivre EJ, McDaniel KF, Albert DH, Mantena SR, Plotnik JP, Wilcox D, Zhang L, Bui MH, Sheppard GS, Wang L, Sehgal V, Lin X, Huang X, Lu X, Uziel T, Hessler P, Lam LT, Bellin RJ, Mehta G, Fidanze S, Pratt JK, Liu D, Hasvold LA, Sun C, Panchal SC, Nicolette JJ, Fossey SL, Park CH, Longenecker K, Bigelow L, Torrent M, Rosenberg SH, Kati WM, Shen Y. Selective inhibition of the BD2 bromodomain of BET proteins in prostate cancer. Nature. 2020 Feb;578(7794):306-310. doi: 10.1038/s41586-020-1930-8. Epub 2020 Jan 22. PMID: 31969702. 2: Fakhar Z, Khan S, AlOmar SY, Alkhuriji A, Ahmad A. ABBV-744 as a potential inhibitor of SARS-CoV-2 main protease enzyme against COVID-19. Sci Rep. 2021 Jan 8;11(1):234. doi: 10.1038/s41598-020-79918-3. PMID: 33420186; PMCID: PMC7794216. 3: Samelson AJ, Tran QD, Robinot R, Carrau L, Rezelj VV, Kain AM, Chen M, Ramadoss GN, Guo X, Lim SA, Lui I, Nuñez JK, Rockwood SJ, Wang J, Liu N, Carlson-Stevermer J, Oki J, Maures T, Holden K, Weissman JS, Wells JA, Conklin BR, TenOever BR, Chakrabarti LA, Vignuzzi M, Tian R, Kampmann M. BRD2 inhibition blocks SARS-CoV-2 infection by reducing transcription of the host cell receptor ACE2. Nat Cell Biol. 2022 Jan;24(1):24-34. doi: 10.1038/s41556-021-00821-8. Epub 2022 Jan 13. PMID: 35027731; PMCID: PMC8820466. 4: Sheppard GS, Wang L, Fidanze SD, Hasvold LA, Liu D, Pratt JK, Park CH, Longenecker K, Qiu W, Torrent M, Kovar PJ, Bui M, Faivre E, Huang X, Lin X, Wilcox D, Zhang L, Shen Y, Albert DH, Magoc TJ, Rajaraman G, Kati WM, McDaniel KF. Discovery of N-Ethyl-4-[2-(4-fluoro-2,6-dimethyl- phenoxy)-5-(1-hydroxy-1-methyl-ethyl)phenyl]-6-methyl-7-oxo-1H-pyrrolo[2, 3-c]pyridine-2-carboxamide (ABBV-744), a BET Bromodomain Inhibitor with Selectivity for the Second Bromodomain. J Med Chem. 2020 May 28;63(10):5585-5623. doi: 10.1021/acs.jmedchem.0c00628. Epub 2020 May 7. PMID: 32324999. 5: Albert DH, Goodwin NC, Davies AM, Rowe J, Feuer G, Boyiadzis M, Dorritie KA, Mancini M, Gandour-Edwards R, Jonas BA, Borthakur G, Aldoss I, Rizzieri DA, Odenike O, Prebet T, Singh S, Popovic R, Shen YU, McDaniel KF, Kati WM, Modi DA, Motwani M, Wolff JE, Frost DJ. Co-clinical Modeling of the Activity of the BET Inhibitor Mivebresib (ABBV-075) in AML. In Vivo. 2022 Jul-Aug;36(4):1615-1627. doi: 10.21873/invivo.12872. PMID: 35738590; PMCID: PMC9301399. 6: Zhang L, Cai T, Lin X, Huang X, Bui MH, Plotnik JP, Bellin RJ, Faivre EJ, Kuruvilla VM, Lam LT, Lu X, Zha Z, Feng W, Hessler P, Uziel T, Zhang Q, Cavazos A, Han L, Ferguson DC, Mehta G, Shanmugavelandy SS, Magoc TJ, Rowe J, Goodwin NC, Dorritie KA, Boyiadzis M, Albert DH, McDaniel KF, Kati WM, Konopleva M, Shen Y. Selective Inhibition of the Second Bromodomain of BET Family Proteins Results in Robust Antitumor Activity in Preclinical Models of Acute Myeloid Leukemia. Mol Cancer Ther. 2021 Oct;20(10):1809-1819. doi: 10.1158/1535-7163.MCT-21-0029. Epub 2021 Jul 12. PMID: 34253595. 7: Vaidergorn MM, da Silva Emery F, Ganesan A. From Hit Seeking to Magic Bullets: The Successful Union of Epigenetic and Fragment Based Drug Discovery (EPIDD + FBDD). J Med Chem. 2021 Oct 14;64(19):13980-14010. doi: 10.1021/acs.jmedchem.1c00787. Epub 2021 Sep 30. PMID: 34591474. 8: Chen J, Li Y, Zhang J, Zhang M, Wei A, Liu H, Xie Z, Ren W, Duan W, Zhang Z, Shen A, Hu Y. Discovery of selective HDAC/BRD4 dual inhibitors as epigenetic probes. Eur J Med Chem. 2021 Jan 1;209:112868. doi: 10.1016/j.ejmech.2020.112868. Epub 2020 Oct 13. PMID: 33077265. 9: Wright S, Hu J, Wang H, Hyle J, Zhang Y, Du G, Konopleva MY, Kornblau SM, Djekidel MN, Rosikiewicz W, Xu B, Lu R, Yang JJ, Li C. Interrogating bromodomain inhibitor resistance in KMT2A-rearranged leukemia through combinatorial CRISPR screens. Proc Natl Acad Sci U S A. 2023 Apr 18;120(16):e2220134120. doi: 10.1073/pnas.2220134120. Epub 2023 Apr 10. PMID: 37036970; PMCID: PMC10120025. 10: Samelson AJ, Tran QD, Robinot R, Carrau L, Rezelj VV, Mac Kain A, Chen M, Ramadoss GN, Guo X, Lim SA, Lui I, Nunez J, Rockwood SJ, Wang J, Liu N, Carlson- Stevermer J, Oki J, Maures T, Holden K, Weissman JS, Wells JA, Conklin BR, TenOever BR, Chakrabarti LA, Vignuzzi M, Tian R, Kampmann M. BRD2 inhibition blocks SARS-CoV-2 infection by reducing transcription of the host cell receptor ACE2. bioRxiv [Preprint]. 2021 Sep 20:2021.01.19.427194. doi: 10.1101/2021.01.19.427194. Update in: Nat Cell Biol. 2022 Jan;24(1):24-34. PMID: 33501440; PMCID: PMC7836110. 11: Rianjongdee F, Atkinson SJ, Chung CW, Grandi P, Gray JRJ, Kaushansky LJ, Medeiros P, Messenger C, Phillipou A, Preston A, Prinjha RK, Rioja I, Satz AL, Taylor S, Wall ID, Watson RJ, Yao G, Demont EH. Discovery of a Highly Selective BET BD2 Inhibitor from a DNA-Encoded Library Technology Screening Hit. J Med Chem. 2021 Aug 12;64(15):10806-10833. doi: 10.1021/acs.jmedchem.1c00412. Epub 2021 Jul 12. PMID: 34251219. 12: Diabate O, Cisse C, Sangare M, Soremekun O, Fatumo S, Shaffer JG, Doumbia S, Wele M. Identification of promising high-affinity inhibitors of SARS-CoV-2 main protease from African Natural Products Databases by Virtual Screening. Res Sq [Preprint]. 2023 Mar 24:rs.3.rs-2673755. doi: 10.21203/rs.3.rs-2673755/v1. PMID: 36993208; PMCID: PMC10055610.