Compounds > ridinilazole
Page last updated: 2024-11-12

ridinilazole

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

Description

ridinilazole: antibiotic [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID16659285
CHEMBL ID3753858
SCHEMBL ID413723
SCHEMBL ID17867397
SCHEMBL ID19235713
MeSH IDM000610521

Synonyms (36)

Synonym
SCHEMBL413723
2,2'-dipyridin-4-yl-1h,1'h-5,5'-bibenzimidazole
2,2'-bis(4-pyridyl)-3h,3'h-5,5'-bibenzimidazole
ridinilazole [who-dd]
06dx01190r ,
unii-06dx01190r
who 10075
smt19969
5,5'-bi-1h-benzimidazole, 2,2'-di-4-pyridinyl-
ridinilazole [usan:inn]
ridinilazole [usan]
ridinilazole [inn]
ridinilazole
308362-25-6
smt-19969
bdbm50134759
CHEMBL3753858 ,
SCHEMBL17867397
CS-6591
HY-16753
2-pyridin-4-yl-6-(2-pyridin-4-yl-3h-benzimidazol-5-yl)-1h-benzimidazole
SCHEMBL19235713
2,2'-di(pyridin-4-yl)-1h,1'h-5,5'-bi(benzimidazole)
DB15308
Q25102246
mfcd28963972
smt19969smt19969
2,2'-di(pyridin-4-yl)-1h,1'h-5,5'-bibenzo[d]imidazole
gtpl10853
D80826
DTXSID101028337
2-(pyridin-4-yl)-6-[2-(pyridin-4-yl)-1h-1,3-benzodiazol-5-yl]-1h-1,3-benzodiazole
LX-0216
IK7 ,
2-pyridin-4-yl-5-(2-pyridin-4-yl-1h-benzimidazol-5-yl)-1h-benzimidazole
AKOS040742551

Research Excerpts

Overview

Ridinilazole (SMT19969) is a narrow-spectrum, non-absorbable antimicrobial with activity against Clostridium difficile undergoing clinical trials.

ExcerptReferenceRelevance
"Ridinilazole is a precision bisbenzimidazole antibiotic being developed to treat CDI and reduce unacceptably high rates of infection recurrence in patients."( The Novel DNA Binding Mechanism of Ridinilazole, a Precision
Alam, MJ; Avis, T; Bassères, E; Begum, K; Coward, C; Duperchy, E; Fox, KR; Gajewski, K; Garey, KW; Hu, C; Mason, CS; Moss, S; Mudaliar, M; Nagalingam, N; Powell, DJ; Reich, S, 2023)		1.91
"Ridinilazole is a novel antibiotic being developed for the treatment of Clostridioides difficile infection (CDI). "( Ridinilazole for the treatment of Clostridioides difficile infection.
Bassères, E; Carlson, TJ; Endres, BT; Garey, KW; Gonzales-Luna, AJ, 2019)		3.4
"Ridinilazole (SMT19969) is a narrow-spectrum, non-absorbable antimicrobial with activity against Clostridium difficile undergoing clinical trials. "( Impact on toxin production and cell morphology in Clostridium difficile by ridinilazole (SMT19969), a novel treatment for C. difficile infection.
Alam, MJ; Bassères, E; Endres, BT; Garey, KW; Khaleduzzaman, M; Miraftabi, F; Vickers, RJ, 2016)		2.11

Toxicity

ExcerptReferenceRelevance
" The majority (88%) of adverse events (AEs) were classified as gastrointestinal disorders and were mild in severity, resolving without treatment."( A randomised phase 1 study to investigate safety, pharmacokinetics and impact on gut microbiota following single and multiple oral doses in healthy male subjects of SMT19969, a novel agent for Clostridium difficile infections.
Best, E; Echols, R; Robinson, N; Tillotson, G; Vickers, R; Wilcox, M, 2015)		0.42
"Oral administration of SMT19969 was considered safe and well tolerated and was associated with negligible plasma concentrations after single and multiple doses."( A randomised phase 1 study to investigate safety, pharmacokinetics and impact on gut microbiota following single and multiple oral doses in healthy male subjects of SMT19969, a novel agent for Clostridium difficile infections.
Best, E; Echols, R; Robinson, N; Tillotson, G; Vickers, R; Wilcox, M, 2015)		0.42

Pharmacokinetics

ExcerptReferenceRelevance
" Pharmacokinetic assessments included blood and faecal sampling."( A randomised phase 1 study to investigate safety, pharmacokinetics and impact on gut microbiota following single and multiple oral doses in healthy male subjects of SMT19969, a novel agent for Clostridium difficile infections.
Best, E; Echols, R; Robinson, N; Tillotson, G; Vickers, R; Wilcox, M, 2015)		0.42

Dosage Studied

ExcerptRelevanceReference
" difficile BI1, treatment with SMT19969, vancomycin and fidaxomicin resulted in 100% survival during the 5 day dosing period, with 90%-100% of animals receiving SMT19969 and fidaxomicin surviving during the post-dosing follow-up period."( SMT19969 for Clostridium difficile infection (CDI): in vivo efficacy compared with fidaxomicin and vancomycin in the hamster model of CDI.
Payne, L; Sattar, A; Thommes, P; Vickers, RJ; Warn, P, 2015)		0.42
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Protein Targets (2)

Inhibition Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
DNA gyrase subunit BStaphylococcus aureusIC50 (µMol)50.00000.00401.50207.7000AID1270519
DNA gyrase subunit AStaphylococcus aureusIC50 (µMol)50.00000.00401.98397.7000AID1270519
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Bioassays (10)

Assay IDTitleYearJournalArticle
AID1270524Inhibition of Staphylococcus aureus topoisomerase 4 assessed as inhibition of decatenation of catenated kinetoplast DNA after 30 mins by agarose gel electrophoresis2015MedChemComm, Aug-05, Volume: 6, Issue:8
The discovery of a novel antibiotic for the treatment of
AID1270513Antibacterial activity against Staphylococcus aureus ATCC 29213 assessed as growth inhibition after 20 hrs by broth dilution method2015MedChemComm, Aug-05, Volume: 6, Issue:8
The discovery of a novel antibiotic for the treatment of
AID1270515Antibacterial activity against Clostridium difficile CD 630 assessed as growth inhibition2015MedChemComm, Aug-05, Volume: 6, Issue:8
The discovery of a novel antibiotic for the treatment of
AID1270519Inhibition of Staphylococcus aureus DNA gyrase assessed as reduction in enzyme-catalyzed supercoiling of relaxed circular pBR322 DNA incubated for 30 mins by agarose gel electrophoresis2015MedChemComm, Aug-05, Volume: 6, Issue:8
The discovery of a novel antibiotic for the treatment of
AID1270521Inhibition of Clostridium difficile DNA gyrase supercoiling activity2015MedChemComm, Aug-05, Volume: 6, Issue:8
The discovery of a novel antibiotic for the treatment of
AID1270520Inhibition of Escherichia coli DNA gyrase supercoiling activity2015MedChemComm, Aug-05, Volume: 6, Issue:8
The discovery of a novel antibiotic for the treatment of
AID1270516Antibacterial activity against Clostridium difficile R20291 assessed as growth inhibition2015MedChemComm, Aug-05, Volume: 6, Issue:8
The discovery of a novel antibiotic for the treatment of
AID1270511Antibacterial activity against Escherichia coli NCTC 10418 assessed as growth inhibition2015MedChemComm, Aug-05, Volume: 6, Issue:8
The discovery of a novel antibiotic for the treatment of
AID1270514Antibacterial activity against clinical isolates of Staphylococcus aureus EMRSA-16 assessed as growth inhibition after 20 hrs by broth dilution method2015MedChemComm, Aug-05, Volume: 6, Issue:8
The discovery of a novel antibiotic for the treatment of
AID1270523Inhibition of Escherichia coli topoisomerase 4-mediated DNA decatenation activity2015MedChemComm, Aug-05, Volume: 6, Issue:8
The discovery of a novel antibiotic for the treatment of
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (18)

TimeframeStudies, This Drug (%)All Drugs %
pre-19900 (0.00)18.7374
1990's0 (0.00)18.2507
2000's0 (0.00)29.6817
2010's13 (72.22)24.3611
2020's5 (27.78)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 37.44

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 strong demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index37.44 (24.57)
Research Supply Index3.09 (2.92)
Research Growth Index4.60 (4.65)
Search Engine Demand Index49.55 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (37.44)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials3 (16.67%)5.53%
Reviews7 (38.89%)6.00%
Case Studies0 (0.00%)4.05%
Observational0 (0.00%)0.25%
Other8 (44.44%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Clinical Trials (4)

Trial Overview

TrialPhaseEnrollmentStudy TypeStart DateStatus
A Phase II, Randomized, Open-Label, Active-Controlled Clinical Study to Investigate the Safety and Efficacy of SMT19969 (200mg BID) for 10 Days Compared With Fidaxomicin (200 mg BID) for 10 Days for the Treatment of Clostridium Difficile Infection (CDI) [NCT02784002]Phase 227 participants (Actual)Interventional2014-12-31Completed
A Phase 3, Randomized, Double-blind, Active Controlled Study to Compare the Efficacy and Safety of Ridinilazole (200 mg, Bid) for 10 Days With Vancomycin (125 mg, Qid) for 10 Days in the Treatment of Clostridium Difficile Infection (CDI) [NCT03595553]Phase 3759 participants (Actual)Interventional2019-01-28Completed
A Phase II, Randomized, Double-Blind, Active-Controlled Clinical Study to Investigate the Efficacy and Safety of SMT19969 Compared With Vancomycin for the Treatment of Clostridium Difficile-Associated Diarrhoea (CDAD) [NCT02092935]Phase 2100 participants (Actual)Interventional2014-04-30Completed
A Randomized, Double Blind, Active Controlled Study to Evaluate the Safety and Tolerability of Ridinilazole Compared With Vancomycin and to Assess the Pharmacokinetics of Ridinilazole in Adolescent Subjects (Aged 12 to <18 Years) With Clostridioides Diffi [NCT04802837]Phase 32 participants (Actual)Interventional2021-05-19Terminated(stopped due to SMT19969-C006 study was terminated in alignment with corporate decision to pursue further development of drug candidate with a partner.)
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Trial Outcomes

TrialOutcome
NCT03595553 (8) [back to overview]Measure of β-diversity of the Gut Microbiota Between Baseline and EOT Stool Samples (Bray-Curtis Index/Dissimilarity).
NCT03595553 (8) [back to overview]Percentage of Change of α-diversity (Shannon Index) of the Microbiota in Stool Samples From Baseline to EOT.
NCT03595553 (8) [back to overview]Clinical Cure
NCT03595553 (8) [back to overview]Clinical Response
NCT03595553 (8) [back to overview]Number of Participants With Sustained Clinical Response (SCR) Defined as Clinical Response and no Recurrence of CDI Through 30 Days Post End of Treatment (EOT).
NCT03595553 (8) [back to overview]Relative Abundance of the 3 Main Bile Acid Groups (Conjugated Primary, Primary and Secondary Bile Acids) From Baseline to EOT.
NCT03595553 (8) [back to overview]Sustained Clinical Response Over 60 Days
NCT03595553 (8) [back to overview]Sustained Clinical Response Over 90 Days
NCT04802837 (1) [back to overview]Incidence and Severity of Treatment-emergant Adverse Events

Measure of β-diversity of the Gut Microbiota Between Baseline and EOT Stool Samples (Bray-Curtis Index/Dissimilarity).

This secondary outcome measures the β-diversity of the gut microbiota in stool samples from baseline to EOT. Bray-Curtis index/dissimilarity measures how different two samples are in the microbiome composition. The Bray-Curtis dissimilarity is graded between 0 and 1, where 0 means the two samples have the same composition (that is they share all the species and every species has the same abundance), and 1 means the two samples do not share any species. (NCT03595553)
Timeframe: Day 10

InterventionBray-Curtis Index (Mean)
Ridinilazole0.7
Vancomycin0.81

[back to top]

Percentage of Change of α-diversity (Shannon Index) of the Microbiota in Stool Samples From Baseline to EOT.

This secondary outcome measures the percentage of change of α-diversity (Shannon Index) of the microbiota in stool samples from baseline to EOT. Shannon index is a weighted statistic measuring both species richness and evenness. The Shannon Index is calculated by taking the relative abundance of each species and sums the relative abundance times the natural log of the relative abundance for each species. The value is converted into a positive value by times minus one. A higher Shannon Index means higher diversity (NCT03595553)
Timeframe: Day 10

Interventionpercent change in Shannon Index (Mean)
Ridinilazole37.06
Vancomycin-7.32

[back to top]

Clinical Cure

defined as the resolution of diarrhea (<3 UBMs in the 1-day period immediately prior to EOT, that is maintained for 2 days after EOT). (NCT03595553)
Timeframe: Day 12

,
InterventionParticipants (Count of Participants)
Clinical CureClinical Cure Failure
Ridinilazole27595
Vancomycin29283

[back to top]

Clinical Response

"defined as~less than 3 unformed bowel movements (UBMs) for consecutive days and maintained through EOT without further CDI treatment at EOT + 2 days, or~the investigator's assessment that the subject no longer needs specific CDI antimicrobial treatment after completion of the course of study medication." (NCT03595553)
Timeframe: Day 12

,
InterventionParticipants (Count of Participants)
Clinical ResponseClinical Response Failure
Ridinilazole32050
Vancomycin34629

[back to top]

Number of Participants With Sustained Clinical Response (SCR) Defined as Clinical Response and no Recurrence of CDI Through 30 Days Post End of Treatment (EOT).

This primary outcome measures the number of participants with Sustained Clinical Response (SCR). SCR is defined as Clinical Response and no recurrence of CDI through 30 days post End of Treatment (EOT). At D40, D70 and D100 the Investigator or medically qualified designee will determine if the patient has a sustained clinical response or experienced RECURRENCE since the previous assessment. The Investigator will assess cure/failure and recurrence based on available information which includes, but is not limited to, improvement from baseline in the number of UBMs, signs & symptoms of CDI, and the requirement for CDI medication. The Investigator should assess cure/failure in a way that best reflects the Investigator's standard clinical practice. (NCT03595553)
Timeframe: Day 40

,
InterventionParticipants (Count of Participants)
SCR based on Clinical CureSCR based on Clinical Cure Failure
Ridinilazole238132
Vancomycin225150

[back to top]

Relative Abundance of the 3 Main Bile Acid Groups (Conjugated Primary, Primary and Secondary Bile Acids) From Baseline to EOT.

This secondary outcome measures the relative abundance of the 3 main Bile Acid Groups (Conjugated Primary, Primary and Secondary Bile Acids) from Baseline to EOT. (NCT03595553)
Timeframe: Day 10

,
Interventionpercentage of abundance (Mean)
Secondary Bile Acid Group at BaselineSecondary Bile Acid Group at EOTPrimary Bile Acid Group at BaselinePrimary Bile Acid Group at EOTConjugated Primary Bile Acid Group at BaselineConjugated Primary Bile Acid Group at EOT
Ridinilazole33.3438.1355.0355.9911.645.88
Vancomycin30.257.8757.4465.7212.3126.42

[back to top]

Sustained Clinical Response Over 60 Days

defined as Clinical Response and no recurrence of CDI through 60 days post EOT (NCT03595553)
Timeframe: Day 70

,
InterventionParticipants (Count of Participants)
Sustained Clinical Response 60 Days Post EOTSustained Clinical Response 60 Days Post EOT Failure
Ridinilazole262108
Vancomycin258117

[back to top]

Sustained Clinical Response Over 90 Days

defined as Clinical Response and no recurrence of CDI through 90 days post EOT (NCT03595553)
Timeframe: Day 100

,
InterventionParticipants (Count of Participants)
Sustained Clinical Response 90 Days Post EOTSustained Clinical Response 90 Days Post EOT Failure
Ridinilazole259111
Vancomycin249126

[back to top]

Incidence and Severity of Treatment-emergant Adverse Events

Safety was assessed using CTCAE v4. (NCT04802837)
Timeframe: Until study completion (Day 100)

InterventionParticipants (Count of Participants)
Ridinilazole0
Vancomycin0

[back to top]
SubstanceRelationship StrengthStudiesTrialsClassesRoles
metronidazole
Metronidazole: A nitroimidazole used to treat AMEBIASIS; VAGINITIS; TRICHOMONAS INFECTIONS; GIARDIASIS; ANAEROBIC BACTERIA; and TREPONEMAL INFECTIONS.. metronidazole : A member of the class of imidazoles substituted at C-1, -2 and -5 with 2-hydroxyethyl, nitro and methyl groups respectively. It has activity against anaerobic bacteria and protozoa, and has a radiosensitising effect on hypoxic tumour cells. It may be given by mouth in tablets, or as the benzoate in an oral suspension. The hydrochloride salt can be used in intravenous infusions. Metronidazole is a prodrug and is selective for anaerobic bacteria due to their ability to intracellularly reduce the nitro group of metronidazole to give nitroso-containing intermediates. These can covalently bind to DNA, disrupting its helical structure, inducing DNA strand breaks and inhibiting bacterial nucleic acid synthesis, ultimately resulting in bacterial cell death.		3.7120C-nitro compound;
imidazoles;
primary alcohol		antiamoebic agent;
antibacterial drug;
antimicrobial agent;
antiparasitic agent;
antitrichomonal drug;
environmental contaminant;
prodrug;
radiosensitizing agent;
xenobiotic
thiophenes
Thiophenes: A monocyclic heteroarene furan in which the oxygen atom is replaced by a sulfur.. thiophenes : Compounds containing at least one thiophene ring.		3.2510mancude organic heteromonocyclic parent;
monocyclic heteroarene;
thiophenes;
volatile organic compound		non-polar solvent
thiazoles
[no description available]		3.25101,3-thiazoles;
mancude organic heteromonocyclic parent;
monocyclic heteroarene
vancomycin
Vancomycin: Antibacterial obtained from Streptomyces orientalis. It is a glycopeptide related to RISTOCETIN that inhibits bacterial cell wall assembly and is toxic to kidneys and the inner ear.. vancomycin : A complex glycopeptide from Streptomyces orientalis. It inhibits a specific step in the synthesis of the peptidoglycan layer in the Gram-positive bacteria Staphylococcus aureus and Clostridium difficile.		7.2352glycopeptideantibacterial drug;
antimicrobial agent;
bacterial metabolite
oxazolidin-2-one
Oxazolidinones: Derivatives of oxazolidin-2-one. They represent an important class of synthetic antibiotic agents.. oxazolidin-2-one : An oxazolidinone that is 1,3-oxazolidine with an oxo substituent at position 2.. oxazolidinone : An oxazolidine containing one or more oxo groups.		4.1520carbamate ester;
oxazolidinone		metabolite
bis-benzimidazole
bis-benzimidazole: in vitro inhibitor of arenavirus synthesis; studied in treatment of lymphocytic choriomeningitis virus infections; also used as its di-HCl salt, A37536; RN given refers to parent cpd with unspecified isomeric designation; structure		8.5110
moxifloxacin
Moxifloxacin: A fluoroquinolone that acts as an inhibitor of DNA TOPOISOMERASE II and is used as a broad-spectrum antibacterial agent.. moxifloxacin : A quinolone that consists of 4-oxo-1,4-dihydroquinoline-3-carboxylic acid bearing a cyclopropyl substituent at position 1, a fluoro substitiuent at position 6, a (4aS,7aS)-octahydro-6H-pyrrolo[3,4-b]pyridin-6-yl group at position 7 and a methoxy substituent at position 8. A member of the fluoroquinolone class of antibacterial agents.		2.1310aromatic ether;
cyclopropanes;
fluoroquinolone antibiotic;
pyrrolidinopiperidine;
quinolinemonocarboxylic acid;
quinolone antibiotic;
quinolone		antibacterial drug
linezolid
[no description available]		2.1310acetamides;
morpholines;
organofluorine compound;
oxazolidinone		antibacterial drug;
protein synthesis inhibitor
stk295900
[no description available]		3.2110
fidaxomicin
Fidaxomicin: A narrow-spectrum macrolide antibacterial agent that is used in the treatment of diarrhea associated with CLOSTRIDIUM DIFFICILE INFECTION.. fidaxomicin : An 18-membered macrolide that is a fermentation product obtained from the Actinomycete Dactylosporangium aurantiacum. A narrow spectrum antibiotic used for treatment of Clostridium difficile-related infections.		3.9630
rep 3123
REP 3123: structure in first source		3.2510
ro13-9904
Ceftriaxone: A broad-spectrum cephalosporin antibiotic and cefotaxime derivative with a very long half-life and high penetrability to meninges, eyes and inner ears.. ceftriaxone : A third-generation cephalosporin compound having 2-(2-amino-1,3-thiazol-4-yl)-2-(methoxyimino)acetylamino and [(2-methyl-5,6-dioxo-1,2,5,6-tetrahydro-1,2,4-triazin-3-yl)sulfanyl]methyl side-groups.		2.1310
lff571
LFF571: an antibacterial agent; structure in first source		3.2510
cadazolid
cadazolid: for treatment of Clostridium difficile infections; structure in first source		4.1520
surotomycin
[no description available]		4.1520
ConditionIndicatedRelationship StrengthStudiesTrials
Clostridioides difficile Infection
[description not available]		015.25153
Clostridium Infections
Infections with bacteria of the genus CLOSTRIDIUM and closely related CLOSTRIDIOIDES species.		112.25153
Recrudescence
[description not available]		03.7430
Health Care Associated Infection
[description not available]		02.1710
Cross Infection
Any infection which a patient contracts in a health-care institution.		02.1710
Disease Models, Animal
Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases.		02.1110
Diarrhea
An increased liquidity or decreased consistency of FECES, such as running stool. Fecal consistency is related to the ratio of water-holding capacity of insoluble solids to total water, rather than the amount of water present. Diarrhea is not hyperdefecation or increased fecal weight.		04.8321