Page last updated: 2024-12-11

hti-286

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

Description

HTI-286: a synthetic analog of the tripeptide hemiasterlin; structure in first source [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID6918637
CHEMBL ID182319
SCHEMBL ID57122
SCHEMBL ID4378011
MeSH IDM0460181

Synonyms (41)

Synonym
phenylhemiasterlin
(e)-(s)-4-{[(s)-3,3-dimethyl-2-((s)-3-methyl-2-methylamino-3-phenyl-butyrylamino)-butyryl]-methyl-amino}-2,5-dimethyl-hex-2-enoic acid
bdbm50150589
(s)-2,5-dimethyl-4-((s)-n,3,3-trimethyl-2-((s)-3-methyl-2-(methylamino)-3-phenylbutanamido)butanamido)hex-2-enoic acid
(s,e)-2,5-dimethyl-4-((s)-n,3,3-trimethyl-2-((s)-3-methyl-2-(methylamino)-3-phenylbutanamido)butanamido)hex-2-enoic acid
4-{[3,3-dimethyl-2-(3-methyl-2-methylamino-3-phenyl-butyrylamino)-butyryl]-methyl-amino}-2,5-dimethyl-hex-2-enoic acid
spa-110
taltobulin
hti-286
D06001
taltobulin (usan/inn)
228266-40-8
l-valinamide, n,beta,beta-trimethyl-l-phenylalanyl-n-((1s,2e)-3-carboxy-1-(1-methylethyl)-2-butenyl)-n,3-dimethyl-
l-valinamide, n,beta,beta-trimethyl-l-phenylalanine-n-((1s,2e)-3-carboxy-1-(1-methylethyl)-2-butenyl)-n,3-dimethyl-
(4s)-4-(((2s)-3,3-dimethyl-2-(((2s)-3-methyl-2-(methylamino)-3-phenylbutanoyl)amino)butanoyl)methylamino)-2,5-dimethylhex-2-enoic acid
hti 286
spa 110
n,beta,beta-trimethyl-l-phenylalanyl-n-[(3s,4e)-5-carboxy-2-methylhex-4-en-3-yl]-n,3-dimethyl-l-valinamide
CHEMBL182319 ,
(e,4s)-4-[[(2s)-3,3-dimethyl-2-[[(2s)-3-methyl-2-(methylamino)-3-phenylbutanoyl]amino]butanoyl]-methylamino]-2,5-dimethylhex-2-enoic acid
unii-j6d6912bxs
taltobulin [usan:inn]
j6d6912bxs ,
(4s)-4-[[(2s)-3,3-dimethyl-2-[[(2s)-3-methyl-2-(methylamino)-3-phenylbutanoyl]amino]butanoyl]methylamino]-2,5-dimethylhex-2-enoic acid
taltobulin [inn]
taltobulin [usan]
l-valinamide,n,.beta.,.beta.-trimethyl-l-phenylalanine-n-((1s,2e)-3-carboxy-1-(1-methylethyl)-2-butenyl)-n,3-dimethyl
CS-3299
HY-15584
SCHEMBL57122
SCHEMBL4378011
CNTMOLDWXSVYKD-PSRNMDMQSA-N
n,beta,beta-trimethyl-l-phenylalanyl-n1-[(1s,2e)-3-carboxy-1-isopropylbut-2-enyl]-n1,3-dimethyl-l-valinamide
DTXSID2041040
NCGC00386600-02
hti-286;spa-110
Q27281267
A911116
(s,e)-4-(((s)-3,3-dimethyl-1-((s)-3-methyl-2-(methylamino)-3-phenylbutanamido)-1-oxobutan-2-yl)(methyl)amino)-2,5-dimethylhex-2-enoic acid
MS-28787
E98768

Research Excerpts

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
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Protein Targets (2)

Potency Measurements

ProteinTaxonomyMeasurementAverage (µ)Min (ref.)Avg (ref.)Max (ref.)Bioassay(s)
cytochrome P450 family 3 subfamily A polypeptide 4Homo sapiens (human)Potency33.78580.01237.983543.2770AID1645841
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Activation Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Tubulin beta-1 chainHomo sapiens (human)Kd0.26000.05800.58941.8600AID238035
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (8)

Processvia Protein(s)Taxonomy
platelet formationTubulin beta-1 chainHomo sapiens (human)
thyroid gland developmentTubulin beta-1 chainHomo sapiens (human)
microtubule polymerizationTubulin beta-1 chainHomo sapiens (human)
spindle assemblyTubulin beta-1 chainHomo sapiens (human)
thyroid hormone transportTubulin beta-1 chainHomo sapiens (human)
platelet aggregationTubulin beta-1 chainHomo sapiens (human)
mitotic cell cycleTubulin beta-1 chainHomo sapiens (human)
microtubule cytoskeleton organizationTubulin beta-1 chainHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (4)

Processvia Protein(s)Taxonomy
GTPase activityTubulin beta-1 chainHomo sapiens (human)
metal ion bindingTubulin beta-1 chainHomo sapiens (human)
structural constituent of cytoskeletonTubulin beta-1 chainHomo sapiens (human)
GTP bindingTubulin beta-1 chainHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (6)

Processvia Protein(s)Taxonomy
cytoplasmTubulin beta-1 chainHomo sapiens (human)
microtubule cytoskeletonTubulin beta-1 chainHomo sapiens (human)
intercellular bridgeTubulin beta-1 chainHomo sapiens (human)
extracellular exosomeTubulin beta-1 chainHomo sapiens (human)
mitotic spindleTubulin beta-1 chainHomo sapiens (human)
microtubuleTubulin beta-1 chainHomo sapiens (human)
cytoplasmTubulin beta-1 chainHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (43)

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.
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.
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.
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.
AID245713Minimum tolerated dose against Lox melanoma human xenograft models in athymic mice2004Bioorganic & medicinal chemistry letters, Nov-01, Volume: 14, Issue:21
Synthesis and activity of novel analogs of hemiasterlin as inhibitors of tubulin polymerization: modification of the A segment.
AID247845Inhibitory concentration against Lox melanoma cells2004Journal of medicinal chemistry, Sep-09, Volume: 47, Issue:19
Synthesis and biological activity of analogues of the antimicrotubule agent N,beta,beta-trimethyl-L-phenylalanyl-N(1)-[(1S,2E)-3-carboxy-1-isopropylbut-2-enyl]- N(1),3-dimethyl-L-valinamide (HTI-286).
AID247728Inhibitory concentration against HCT-15 cells was evaluated2004Journal of medicinal chemistry, Sep-09, Volume: 47, Issue:19
Synthesis and biological activity of analogues of the antimicrotubule agent N,beta,beta-trimethyl-L-phenylalanyl-N(1)-[(1S,2E)-3-carboxy-1-isopropylbut-2-enyl]- N(1),3-dimethyl-L-valinamide (HTI-286).
AID252005Percent inhibition of bovine microtubule-assisted protein (MAP) rich tubulin polymerisation at concentration of 0.3 uM2004Bioorganic & medicinal chemistry letters, Nov-01, Volume: 14, Issue:21
Synthesis and activity of novel analogs of hemiasterlin as inhibitors of tubulin polymerization: modification of the A segment.
AID248618Compound was tested for the cytotoxicity against KB-8-5 cell line expressing P-glycoprotein; value ranges from 1.2-5 nM2004Bioorganic & medicinal chemistry letters, Aug-16, Volume: 14, Issue:16
Tubulin inhibitors. Synthesis and biological activity of HTI-286 analogs with B-segment heterosubstituents.
AID247858Concentration required to inhibit tumor cell growth in KB-3-1 cells2004Journal of medicinal chemistry, Sep-09, Volume: 47, Issue:19
Synthesis and biological activity of analogues of the antimicrotubule agent N,beta,beta-trimethyl-L-phenylalanyl-N(1)-[(1S,2E)-3-carboxy-1-isopropylbut-2-enyl]- N(1),3-dimethyl-L-valinamide (HTI-286).
AID248889Concentration required to kill human epidermoid KBV1 cell lines containing very high levels of P-glycoprotein after 3 days of continuous exposure2004Bioorganic & medicinal chemistry letters, Nov-01, Volume: 14, Issue:21
Synthesis and activity of novel analogs of hemiasterlin as inhibitors of tubulin polymerization: modification of the A segment.
AID244785Minimum effective dose was evaluated in lox melanoma human tumor graft model in athymic mice when administered intravenously2004Journal of medicinal chemistry, Sep-09, Volume: 47, Issue:19
Synthesis and biological activity of analogues of the antimicrotubule agent N,beta,beta-trimethyl-L-phenylalanyl-N(1)-[(1S,2E)-3-carboxy-1-isopropylbut-2-enyl]- N(1),3-dimethyl-L-valinamide (HTI-286).
AID331685Antiproliferative activity against human 1A9 cells2008Bioorganic & medicinal chemistry letters, May-01, Volume: 18, Issue:9
Tubulysin analogs incorporating desmethyl and dimethyl tubuphenylalanine derivatives.
AID249650Effect at 1.6 mpk against DLD1 cell line expressing P-glycoprotein transporter in athymic mice; Active2004Bioorganic & medicinal chemistry letters, Nov-01, Volume: 14, Issue:21
Synthesis and activity of novel analogs of hemiasterlin as inhibitors of tubulin polymerization: modification of the A segment.
AID331686Inhibition of rat brain tubulin polymerization2008Bioorganic & medicinal chemistry letters, May-01, Volume: 18, Issue:9
Tubulysin analogs incorporating desmethyl and dimethyl tubuphenylalanine derivatives.
AID411786Antiproliferative activity against human MCF7 cells after 4 days by SRB assay2009Journal of medicinal chemistry, Jan-22, Volume: 52, Issue:2
Total synthesis and biological evaluation of tubulysin U, tubulysin V, and their analogues.
AID251729Compound was evaluated for the inhibition of MAP-rich tubulin polymerisation at 0.3 uM2004Bioorganic & medicinal chemistry letters, Aug-16, Volume: 14, Issue:16
Tubulin inhibitors. Synthesis and biological activity of HTI-286 analogs with B-segment heterosubstituents.
AID247685Inhibitory concentration against KM20 cells was evaluated2004Journal of medicinal chemistry, Sep-09, Volume: 47, Issue:19
Synthesis and biological activity of analogues of the antimicrotubule agent N,beta,beta-trimethyl-L-phenylalanyl-N(1)-[(1S,2E)-3-carboxy-1-isopropylbut-2-enyl]- N(1),3-dimethyl-L-valinamide (HTI-286).
AID248620Compound was tested for the cytotoxicity against KB-V1 cell line expressing P-glycoprotein; value ranges from 40-140 nM2004Bioorganic & medicinal chemistry letters, Aug-16, Volume: 14, Issue:16
Tubulin inhibitors. Synthesis and biological activity of HTI-286 analogs with B-segment heterosubstituents.
AID411785Antiproliferative activity against human 1A9 cells after 4 days by SRB assay2009Journal of medicinal chemistry, Jan-22, Volume: 52, Issue:2
Total synthesis and biological evaluation of tubulysin U, tubulysin V, and their analogues.
AID251767Compound was evaluated for the ability to inhibit cell-free tubulin polymerisation at 0.5 uM2004Bioorganic & medicinal chemistry letters, Aug-16, Volume: 14, Issue:16
D-piece modifications of the hemiasterlin analog HTI-286 produce potent tubulin inhibitors.
AID245717Minimum tolerated dose was evaluated in lox melanoma human tumor graft model in athymic mice when administered intravenously2004Journal of medicinal chemistry, Sep-09, Volume: 47, Issue:19
Synthesis and biological activity of analogues of the antimicrotubule agent N,beta,beta-trimethyl-L-phenylalanyl-N(1)-[(1S,2E)-3-carboxy-1-isopropylbut-2-enyl]- N(1),3-dimethyl-L-valinamide (HTI-286).
AID248401Compound was tested for cytotoxicity against paclitaxel resistant KB-8-5 cell line expressing P-glycoprotein2004Bioorganic & medicinal chemistry letters, Aug-16, Volume: 14, Issue:16
D-piece modifications of the hemiasterlin analog HTI-286 produce potent tubulin inhibitors.
AID247787Inhibitory concentration against NCI-H1299 cells was evaluated2004Journal of medicinal chemistry, Sep-09, Volume: 47, Issue:19
Synthesis and biological activity of analogues of the antimicrotubule agent N,beta,beta-trimethyl-L-phenylalanyl-N(1)-[(1S,2E)-3-carboxy-1-isopropylbut-2-enyl]- N(1),3-dimethyl-L-valinamide (HTI-286).
AID249651Effect at 1.6 mpk against MX1W cell line expressing P-glycoprotein transporter in athymic mice; Active2004Bioorganic & medicinal chemistry letters, Nov-01, Volume: 14, Issue:21
Synthesis and activity of novel analogs of hemiasterlin as inhibitors of tubulin polymerization: modification of the A segment.
AID247640Inhibitory concentration against S1 cells was evaluated2004Journal of medicinal chemistry, Sep-09, Volume: 47, Issue:19
Synthesis and biological activity of analogues of the antimicrotubule agent N,beta,beta-trimethyl-L-phenylalanyl-N(1)-[(1S,2E)-3-carboxy-1-isopropylbut-2-enyl]- N(1),3-dimethyl-L-valinamide (HTI-286).
AID326224Cytotoxicity against human 1A9 cells2008Journal of medicinal chemistry, Mar-27, Volume: 51, Issue:6
Cytotoxic simplified tubulysin analogues.
AID354406Cytotoxicity activity against human MCF7 cells expressing p53 mutant by MTT assay2003Journal of natural products, Feb, Volume: 66, Issue:2
Synthesis and antimitotic/cytotoxic activity of hemiasterlin analogues.
AID326225Inhibition of rat brain tubulin polymerization2008Journal of medicinal chemistry, Mar-27, Volume: 51, Issue:6
Cytotoxic simplified tubulysin analogues.
AID248081Compound was tested for the cytotoxicity against KB-3-1 cell line; value ranges from 0.6-2 nM2004Bioorganic & medicinal chemistry letters, Aug-16, Volume: 14, Issue:16
Tubulin inhibitors. Synthesis and biological activity of HTI-286 analogs with B-segment heterosubstituents.
AID411787Inhibition of tubulin polymerization2009Journal of medicinal chemistry, Jan-22, Volume: 52, Issue:2
Total synthesis and biological evaluation of tubulysin U, tubulysin V, and their analogues.
AID248380Compound was tested for cytotoxicity against paclitaxel resistant KB-V1 cell line expressing P-glycoprotein2004Bioorganic & medicinal chemistry letters, Aug-16, Volume: 14, Issue:16
D-piece modifications of the hemiasterlin analog HTI-286 produce potent tubulin inhibitors.
AID354405Antimitotic activity against human MCF7 cells expressing p53 mutant by MTT assay2003Journal of natural products, Feb, Volume: 66, Issue:2
Synthesis and antimitotic/cytotoxic activity of hemiasterlin analogues.
AID247853Compound was tested for cytotoxicity against paclitaxel sensitive KB-3-1 cell line2004Bioorganic & medicinal chemistry letters, Aug-16, Volume: 14, Issue:16
D-piece modifications of the hemiasterlin analog HTI-286 produce potent tubulin inhibitors.
AID251815Percent inhibition of tubulin polymerization at 0.3 uM concentration2004Journal of medicinal chemistry, Sep-09, Volume: 47, Issue:19
Synthesis and biological activity of analogues of the antimicrotubule agent N,beta,beta-trimethyl-L-phenylalanyl-N(1)-[(1S,2E)-3-carboxy-1-isopropylbut-2-enyl]- N(1),3-dimethyl-L-valinamide (HTI-286).
AID244780Minimum effective dose against Lox melanoma human xenograft models in athymic mice2004Bioorganic & medicinal chemistry letters, Nov-01, Volume: 14, Issue:21
Synthesis and activity of novel analogs of hemiasterlin as inhibitors of tubulin polymerization: modification of the A segment.
AID247859Concentration required to inhibit tumor cell growth in KB-8-5 cells2004Journal of medicinal chemistry, Sep-09, Volume: 47, Issue:19
Synthesis and biological activity of analogues of the antimicrotubule agent N,beta,beta-trimethyl-L-phenylalanyl-N(1)-[(1S,2E)-3-carboxy-1-isopropylbut-2-enyl]- N(1),3-dimethyl-L-valinamide (HTI-286).
AID248904Concentration required to kill human epidermoid KB-3-1 cell lines containing very low levels of P-glycoprotein after 3 days of continuous exposure2004Bioorganic & medicinal chemistry letters, Nov-01, Volume: 14, Issue:21
Synthesis and activity of novel analogs of hemiasterlin as inhibitors of tubulin polymerization: modification of the A segment.
AID249654Effect at 1.6 mpk against HCT-15 cell line expressing P-glycoprotein transporter in athymic mice; Active2004Bioorganic & medicinal chemistry letters, Nov-01, Volume: 14, Issue:21
Synthesis and activity of novel analogs of hemiasterlin as inhibitors of tubulin polymerization: modification of the A segment.
AID248874Concentration required to kill human epidermoid KB85 cell lines containing moderate levels of P-glycoprotein after 3 days of continuous exposure2004Bioorganic & medicinal chemistry letters, Nov-01, Volume: 14, Issue:21
Synthesis and activity of novel analogs of hemiasterlin as inhibitors of tubulin polymerization: modification of the A segment.
AID247837Concentration required to inhibit tumor cell growth in KB-V1 cells2004Journal of medicinal chemistry, Sep-09, Volume: 47, Issue:19
Synthesis and biological activity of analogues of the antimicrotubule agent N,beta,beta-trimethyl-L-phenylalanyl-N(1)-[(1S,2E)-3-carboxy-1-isopropylbut-2-enyl]- N(1),3-dimethyl-L-valinamide (HTI-286).
AID238035Binding affinity towards tubulin2004Journal of medicinal chemistry, Sep-09, Volume: 47, Issue:19
Synthesis and biological activity of analogues of the antimicrotubule agent N,beta,beta-trimethyl-L-phenylalanyl-N(1)-[(1S,2E)-3-carboxy-1-isopropylbut-2-enyl]- N(1),3-dimethyl-L-valinamide (HTI-286).
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (27)

TimeframeStudies, This Drug (%)All Drugs %
pre-19900 (0.00)18.7374
1990's0 (0.00)18.2507
2000's20 (74.07)29.6817
2010's5 (18.52)24.3611
2020's2 (7.41)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 10.89

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 Index10.89 (24.57)
Research Supply Index3.40 (2.92)
Research Growth Index4.29 (4.65)
Search Engine Demand Index0.00 (26.88)
Search Engine Supply Index0.00 (0.95)

This Compound (10.89)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials2 (7.41%)5.53%
Reviews1 (3.70%)6.00%
Case Studies0 (0.00%)4.05%
Observational0 (0.00%)0.25%
Other24 (88.89%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]