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n-(3,4-difluoro-2-(2-fluoro-4-iodophenylamino)-6-methoxyphenyl)-1-(2,3-dihydroxypropyl)cyclopropane-1-sulfonamide

Description Research Excerpts Clinical Trials Roles Classes Pathways Study Profile Bioassays Related Drugs Related Conditions Protein Interactions Research Growth Market Indicators

Description

N-(3,4-difluoro-2-(2-fluoro-4-iodophenylamino)-6-methoxyphenyl)-1-(2,3-dihydroxypropyl)cyclopropane-1-sulfonamide: a MEK inhibitor; structure in first source [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID15985330
CHEMBL ID3349342
SCHEMBL ID345334
SCHEMBL ID10314890
MeSH IDM0540807

Synonyms (15)

Synonym
n-(3,4-difluoro-2-(2-fluoro-4-iodophenylamino)-6-methoxyphenyl)-1-(2,3-dihydroxypropyl)cyclopropane-1-sulfonamide
NCGC00229510-01
SCHEMBL345334
n-(3,4-difluoro-2-(2-fluoro-4-iodophenylamino)-6-methoxyphenyl)-1-(2,3-dihydroxypropyl) cyclopropane-1-sulfonamide
RDSACQWTXKSHJT-UHFFFAOYSA-N
SCHEMBL10314890
CHEMBL3349342
HMS3654O17
NCGC00229510-02
bay 869766;rdea119
SB16881
n-[3,4-difluoro-2-(2-fluoro-4-iodoanilino)-6-methoxyphenyl]-1-(2,3-dihydroxypropyl)cyclopropane-1-sulfonamide
refametinib r-enantiomer
nsc-765866
nsc765866

Research Excerpts

Toxicity

ExcerptReferenceRelevance
" Most frequent drug-related adverse events were diarrhea, rash, aspartate aminotransferase elevation, vomiting, and nausea."( A phase II study of the efficacy and safety of the combination therapy of the MEK inhibitor refametinib (BAY 86-9766) plus sorafenib for Asian patients with unresectable hepatocellular carcinoma.
Choi, HJ; Heo, J; Hsieh, WS; Hsu, C; Jeffers, M; Kappeler, C; Krissel, H; Lim, HY; Lin, CY; Park, JW; Poon, RT; Rajagopalan, P; Rau, KM; Tak, WY; Tay, MH; Yen, CJ; Yeo, W; Yoon, JH, 2014
)
0.4
" Frequent dose modifications due to grade 3 adverse events may have contributed to limited treatment effect."( A phase II study of the efficacy and safety of the combination therapy of the MEK inhibitor refametinib (BAY 86-9766) plus sorafenib for Asian patients with unresectable hepatocellular carcinoma.
Choi, HJ; Heo, J; Hsieh, WS; Hsu, C; Jeffers, M; Kappeler, C; Krissel, H; Lim, HY; Lin, CY; Park, JW; Poon, RT; Rajagopalan, P; Rau, KM; Tak, WY; Tay, MH; Yen, CJ; Yeo, W; Yoon, JH, 2014
)
0.4

Pharmacokinetics

ExcerptReferenceRelevance
" Plasma levels of refametinib, refametinib metabolite M17, and sorafenib were measured for pharmacokinetic assessments."( A Phase I Study of the Safety, Pharmacokinetics, and Pharmacodynamics of Combination Therapy with Refametinib plus Sorafenib in Patients with Advanced Cancer.
Adjei, AA; Becerra, CH; Braiteh, F; Clendeninn, NJ; El-Khoueiry, A; Garbo, L; Gunawan, S; Hezel, AF; Iverson, C; Krissel, H; Leffingwell, DP; Manhard, KJ; Miner, JN; Rajagopalan, P; Richards, DA; Shen, Z; Sherman, M; Stephenson, JJ; Wilson, DM; Yeh, LT, 2016
)
0.43
" Refametinib was readily absorbed following oral administration (plasma half-life of ∼16 hours at the MTD), and pharmacokinetic parameters displayed near-dose proportionality, with less than 2-fold accumulation after multiple dosing."( A Phase I Study of the Safety, Pharmacokinetics, and Pharmacodynamics of Combination Therapy with Refametinib plus Sorafenib in Patients with Advanced Cancer.
Adjei, AA; Becerra, CH; Braiteh, F; Clendeninn, NJ; El-Khoueiry, A; Garbo, L; Gunawan, S; Hezel, AF; Iverson, C; Krissel, H; Leffingwell, DP; Manhard, KJ; Miner, JN; Rajagopalan, P; Richards, DA; Shen, Z; Sherman, M; Stephenson, JJ; Wilson, DM; Yeh, LT, 2016
)
0.43

Compound-Compound Interactions

ExcerptReferenceRelevance
" The effects of RDEA119/BAY 869766 as a single agent and in combination with rapamycin were studied in 3 early passage primary pancreatic cancer xenografts, OCIP19, 21, and 23, grown orthotopically."( Antitumour activity of a potent MEK inhibitor RDEA119/BAY 869766 combined with rapamycin in human orthotopic primary pancreatic cancer xenografts.
Chang, Q; Chapman, MS; Hedley, DW; Miner, JN, 2010
)
0.36
"RDEA119/BAY 869766 alone or in combination with rapamycin showed significant growth inhibition in all the 3 models, with a significant decrease in the percentage of cells in S-phase, accompanied by a large decrease in bromodeoxyuridine labelling and cell cycle arrest predominantly in G1."( Antitumour activity of a potent MEK inhibitor RDEA119/BAY 869766 combined with rapamycin in human orthotopic primary pancreatic cancer xenografts.
Chang, Q; Chapman, MS; Hedley, DW; Miner, JN, 2010
)
0.36
"The objectives of the study were to evaluate the allosteric mitogen-activated protein kinase kinase (MEK) inhibitor BAY 86-9766 in monotherapy and in combination with sorafenib in orthotopic and subcutaneous hepatocellular carcinoma (HCC) models with different underlying etiologies in two species."( Allosteric MEK1/2 inhibitor refametinib (BAY 86-9766) in combination with sorafenib exhibits antitumor activity in preclinical murine and rat models of hepatocellular carcinoma.
Adjei, AA; Kissel, M; Miner, JN; Mumberg, D; Neuhaus, R; Puehler, F; Schmieder, R; Scholz, A; Ziegelbauer, K, 2013
)
0.39
" Synergistic effects in combination with sorafenib were shown in Huh-7, Hep3B xenografts, and MH3924A allografts."( Allosteric MEK1/2 inhibitor refametinib (BAY 86-9766) in combination with sorafenib exhibits antitumor activity in preclinical murine and rat models of hepatocellular carcinoma.
Adjei, AA; Kissel, M; Miner, JN; Mumberg, D; Neuhaus, R; Puehler, F; Schmieder, R; Scholz, A; Ziegelbauer, K, 2013
)
0.39
"BAY 86-9766 shows potent single-agent antitumor activity and acts synergistically in combination with sorafenib in preclinical HCC models."( Allosteric MEK1/2 inhibitor refametinib (BAY 86-9766) in combination with sorafenib exhibits antitumor activity in preclinical murine and rat models of hepatocellular carcinoma.
Adjei, AA; Kissel, M; Miner, JN; Mumberg, D; Neuhaus, R; Puehler, F; Schmieder, R; Scholz, A; Ziegelbauer, K, 2013
)
0.39

Bioavailability

ExcerptReferenceRelevance
"The ATP-binding cassette transporter P-glycoprotein (P-gp) is known to limit both brain penetration and oral bioavailability of many chemotherapy drugs."( A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein.
Ambudkar, SV; Brimacombe, KR; Chen, L; Gottesman, MM; Guha, R; Hall, MD; Klumpp-Thomas, C; Lee, OW; Lee, TD; Lusvarghi, S; Robey, RW; Shen, M; Tebase, BG, 2019
)
0.51

Dosage Studied

ExcerptRelevanceReference
" Using pharmacokinetic and pharmacodynamic data, we show that maintaining adequate MEK inhibition throughout the dosing interval is likely more important than achieving high peak levels because greater efficacy was achieved with more frequent but lower dosing."( RDEA119/BAY 869766: a potent, selective, allosteric inhibitor of MEK1/2 for the treatment of cancer.
Appleby, T; Dadson, C; Hamatake, R; Iverson, C; Lai, C; Larson, G; Maderna, A; Miner, JN; Quart, B; Vernier, JM; Vo, T; Weingarten, P; Yeh, LT, 2009
)
0.35
" Continuous daily dosing resulted in moderate accumulation at most dose levels."( Multicenter phase I trial of the mitogen-activated protein kinase 1/2 inhibitor BAY 86-9766 in patients with advanced cancer.
Adjei, AA; Clendeninn, NJ; Dubowy, RL; Dy, GK; Eckhardt, SG; Gore, L; Iverson, C; Jeffers, M; Leffingwell, DP; Lewis, KD; Ma, WW; Miner, JN; Rajagopalan, P; Ramanathan, RK; Sheedy, B; Shen, Z; Von Hoff, DD; Weekes, CD; Weiss, GJ; Yeh, LT, 2013
)
0.39
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Bioassays (6)

Assay IDTitleYearJournalArticle
AID1296008Cytotoxic Profiling of Annotated Libraries Using Quantitative High-Throughput Screening2020SLAS discovery : advancing life sciences R & D, 01, Volume: 25, Issue:1
Cytotoxic Profiling of Annotated and Diverse Chemical Libraries Using Quantitative High-Throughput Screening.
AID1347160Primary screen NINDS Rhodamine qHTS for Zika virus inhibitors2020Proceedings of the National Academy of Sciences of the United States of America, 12-08, Volume: 117, Issue:49
Therapeutic candidates for the Zika virus identified by a high-throughput screen for Zika protease inhibitors.
AID1346986P-glycoprotein substrates identified in KB-3-1 adenocarcinoma cell line, qHTS therapeutic library screen2019Molecular pharmacology, 11, Volume: 96, Issue:5
A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein.
AID1347159Primary screen GU Rhodamine qHTS for Zika virus inhibitors: Unlinked NS2B-NS3 protease assay2020Proceedings of the National Academy of Sciences of the United States of America, 12-08, Volume: 117, Issue:49
Therapeutic candidates for the Zika virus identified by a high-throughput screen for Zika protease inhibitors.
AID1346987P-glycoprotein substrates identified in KB-8-5-11 adenocarcinoma cell line, qHTS therapeutic library screen2019Molecular pharmacology, 11, Volume: 96, Issue:5
A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein.
AID686947qHTS for small molecule inhibitors of Yes1 kinase: Primary Screen2013Bioorganic & medicinal chemistry letters, Aug-01, Volume: 23, Issue:15
Identification of potent Yes1 kinase inhibitors using a library screening approach.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (29)

TimeframeStudies, This Drug (%)All Drugs %
pre-19900 (0.00)18.7374
1990's0 (0.00)18.2507
2000's1 (3.45)29.6817
2010's25 (86.21)24.3611
2020's3 (10.34)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 11.98

According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be weak demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index11.98 (24.57)
Research Supply Index3.58 (2.92)
Research Growth Index5.57 (4.65)
Search Engine Demand Index0.00 (26.88)
Search Engine Supply Index0.00 (0.95)

This Compound (11.98)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials5 (16.67%)5.53%
Reviews2 (6.67%)6.00%
Case Studies1 (3.33%)4.05%
Observational0 (0.00%)0.25%
Other22 (73.33%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]