TMC-310911

Identification

Generic Name
TMC-310911
DrugBank Accession Number
DB15623
Background

TMC-310911 (also known as ASC-09) is a novel investigational protease inhibitor (PI) that is structurally similar to the currently available darunavir.4 It is being investigated for use in HIV-1 infections. TMC-310911 has shown marked activity against a variety of HIV-1 strains, including multi-PI-resistant strains, and may be less likely to generate resistance, making it a potentially desirable therapy for both treatment-naive and PI-experienced patients.4,3

TMC-310911 is currently being investigated, in combination with other HIV therapies and antivirals, as a potential treatment for COVID-19 caused by SARS-CoV-2.5

Type
Small Molecule
Groups
Investigational
Structure
Weight
Average: 755.987
Monoisotopic: 755.338640455
Chemical Formula
C38H53N5O7S2
Synonyms
Not Available
External IDs
  • ASC-09
  • TMC 310911
  • TMC-310911
  • TMC310911

Pharmacology

Indication

Not Available

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Contraindications & Blackbox Warnings
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Pharmacodynamics

Not Available

Mechanism of action
TargetActionsOrganism
UHIV-1 protease
inhibitor
Human Immunodeficiency Virus
Absorption

Not Available

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism
Not Available
Route of elimination

Not Available

Half-life

Not Available

Clearance

Not Available

Adverse Effects
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Toxicity

Not Available

Pathways
Not Available
Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
Not Available

Interactions

Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
Adenovirus type 7 vaccine liveThe therapeutic efficacy of Adenovirus type 7 vaccine live can be decreased when used in combination with TMC-310911.
AlmasilateAlmasilate can cause a decrease in the absorption of TMC-310911 resulting in a reduced serum concentration and potentially a decrease in efficacy.
AlprazolamThe serum concentration of Alprazolam can be increased when it is combined with TMC-310911.
AluminiumAluminium can cause a decrease in the absorption of TMC-310911 resulting in a reduced serum concentration and potentially a decrease in efficacy.
Aluminium phosphateAluminium phosphate can cause a decrease in the absorption of TMC-310911 resulting in a reduced serum concentration and potentially a decrease in efficacy.
Food Interactions
Not Available

Categories

Drug Categories
Classification
Not classified
Affected organisms
  • Human immunodeficiency virus 1
  • SARS-CoV-2

Chemical Identifiers

UNII
0151W500HP
CAS number
1000287-05-7
InChI Key
JQUNFHFWXCXPRK-AMMMHQJVSA-N
InChI
InChI=1S/C38H53N5O7S2/c1-25(2)22-43(23-33(44)32(20-26-8-4-3-5-9-26)41-38(45)50-34-24-49-36-30(34)16-19-48-36)52(46,47)29-12-13-31-35(21-29)51-37(40-31)39-27-14-17-42(18-15-27)28-10-6-7-11-28/h3-5,8-9,12-13,21,25,27-28,30,32-34,36,44H,6-7,10-11,14-20,22-24H2,1-2H3,(H,39,40)(H,41,45)/t30-,32-,33+,34-,36+/m0/s1
IUPAC Name
(3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yl N-[(2S,3R)-3-hydroxy-4-[N-(2-methylpropyl)2-[(1-cyclopentylpiperidin-4-yl)amino]-1,3-benzothiazole-6-sulfonamido]-1-phenylbutan-2-yl]carbamate
SMILES
[H][C@@]12CCO[C@]1([H])OC[C@@H]2OC(=O)N[C@@H](CC1=CC=CC=C1)[C@H](O)CN(CC(C)C)S(=O)(=O)C1=CC=C2N=C(NC3CCN(CC3)C3CCCC3)SC2=C1

References

General References
  1. Dierynck I, Van Marck H, Van Ginderen M, Jonckers TH, Nalam MN, Schiffer CA, Raoof A, Kraus G, Picchio G: TMC310911, a novel human immunodeficiency virus type 1 protease inhibitor, shows in vitro an improved resistance profile and higher genetic barrier to resistance compared with current protease inhibitors. Antimicrob Agents Chemother. 2011 Dec;55(12):5723-31. doi: 10.1128/AAC.00748-11. Epub 2011 Sep 6. [Article]
  2. Hoetelmans RM, Dierynck I, Smyej I, Meyvisch P, Jacquemyn B, Marien K, Simmen K, Verloes R: Safety and pharmacokinetics of the HIV-1 protease inhibitor TMC310911 coadministered with ritonavir in healthy participants: results from 2 phase 1 studies. J Acquir Immune Defic Syndr. 2014 Mar 1;65(3):299-305. doi: 10.1097/QAI.0000000000000011. [Article]
  3. Stellbrink HJ, Arasteh K, Schurmann D, Stephan C, Dierynck I, Smyej I, Hoetelmans RM, Truyers C, Meyvisch P, Jacquemyn B, Marien K, Simmen K, Verloes R: Antiviral activity, pharmacokinetics, and safety of the HIV-1 protease inhibitor TMC310911, coadministered with ritonavir, in treatment-naive HIV-1-infected patients. J Acquir Immune Defic Syndr. 2014 Mar 1;65(3):283-9. doi: 10.1097/QAI.0000000000000003. [Article]
  4. NIH AIDSinfo: TMC-310911 Pharmacology [Link]
  5. Nature Biotechnology: Coronavirus puts drug repurposing on the fast track [Link]
ChemSpider
34554561
ZINC
ZINC000098208561
PDBe Ligand
74T
PDB Entries
3r4b

Clinical Trials

Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
PhaseStatusPurposeConditionsCount
2CompletedTreatmentHuman Immunodeficiency Virus Type 1 (HIV-1)1
1WithdrawnTreatmentHuman Immunodeficiency Virus (HIV) Infections1
Not AvailableTerminatedTreatmentCoronavirus Disease 2019 (COVID‑19)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00544 mg/mLALOGPS
logP4.5ALOGPS
logP5.32Chemaxon
logS-5.1ALOGPS
pKa (Strongest Acidic)13.46Chemaxon
pKa (Strongest Basic)9.02Chemaxon
Physiological Charge1Chemaxon
Hydrogen Acceptor Count9Chemaxon
Hydrogen Donor Count3Chemaxon
Polar Surface Area142.56 Å2Chemaxon
Rotatable Bond Count14Chemaxon
Refractivity200.24 m3·mol-1Chemaxon
Polarizability80.09 Å3Chemaxon
Number of Rings7Chemaxon
Bioavailability0Chemaxon
Rule of FiveNoChemaxon
Ghose FilterNoChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleYesChemaxon
Predicted ADMET Features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-0udi-0001043900-533dc6309c21a0a101db
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-0a4u-0020079800-fd4731953550887051d1
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-03dl-4119406200-09a44b3f5a0598095db5
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-08fr-0629023800-39d7af502a46822aec74
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-0ikd-3297103300-ac43c2bf262c551160da
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-06r2-7338219500-4f3cbb633198dcfc5f8f
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-252.08955
predicted
DeepCCS 1.0 (2019)
[M+H]+254.25485
predicted
DeepCCS 1.0 (2019)
[M+Na]+260.3187
predicted
DeepCCS 1.0 (2019)

Targets

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Kind
Protein
Organism
Human Immunodeficiency Virus
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Aspartic-type endopeptidase activity
Specific Function
Not Available
Gene Name
HIV-1 protease
Uniprot ID
O90777
Uniprot Name
HIV-1 protease
Molecular Weight
10724.61 Da
References
  1. Hoetelmans RM, Dierynck I, Smyej I, Meyvisch P, Jacquemyn B, Marien K, Simmen K, Verloes R: Safety and pharmacokinetics of the HIV-1 protease inhibitor TMC310911 coadministered with ritonavir in healthy participants: results from 2 phase 1 studies. J Acquir Immune Defic Syndr. 2014 Mar 1;65(3):299-305. doi: 10.1097/QAI.0000000000000011. [Article]
  2. Dierynck I, Van Marck H, Van Ginderen M, Jonckers TH, Nalam MN, Schiffer CA, Raoof A, Kraus G, Picchio G: TMC310911, a novel human immunodeficiency virus type 1 protease inhibitor, shows in vitro an improved resistance profile and higher genetic barrier to resistance compared with current protease inhibitors. Antimicrob Agents Chemother. 2011 Dec;55(12):5723-31. doi: 10.1128/AAC.00748-11. Epub 2011 Sep 6. [Article]

Drug created at March 04, 2020 17:20 / Updated at June 12, 2020 16:53