Delving into the Latest Updates on LY-2623091 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

MR

Action

antagonists

Mechanism

MR antagonists(Mineralocorticoid receptor antagonists)

Therapeutic Areas

Cardiovascular DiseasesUrogenital Diseases

Active Indication-

Inactive Indication

Chronic Kidney DiseasesEssential Hypertension

Originator Organization

Eli Lilly & Co.

Active Organization-

Inactive Organization

Eli Lilly & Co.

License Organization-

Drug Highest PhasePendingPhase 2

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC30H30FN5O3

InChIKeyYPCLDHGBEKZGEB-RUDKWAFVSA-N

CAS Registry1162264-07-4

The first purpose of this study is to evaluate the effect of itraconazole (and possibly diltiazem) on the amount of LY2623091 in the blood stream and how long the body takes to get rid of it.
The second purpose of the study is to evaluate the effect of LY2623091 on the amount of simvastatin (and possibly tadalafil) in the blood stream and how long the body takes to get rid of it.
The safety and tolerability of LY2623091 when given with itraconazole, simvastatin and diltiazem or tadalafil will be evaluated.
There will be three groups of participants in this study. Results from Groups 1 and 2 will be analyzed during the study to determine whether to enroll participants in Group 3 or 4. The study is expected to last up to 40 days from the first dose to follow-up (inclusive). Screening may occur up to 28 days prior to enrollment.

Start Date01 Nov 2014

Sponsor / Collaborator

Eli Lilly & Co.

NCT02242981

/ CompletedPhase 1

Disposition of [14C]-LY2623091 Following Oral Administration in Healthy Subjects

This type of study is called a radiolabeled study. For this study, LY2623091 (study drug) has been specially prepared to contain radiolabeled carbon [^14C]. [^14C] is a naturally occurring radioactive form of the element, carbon. This study will increase understanding about how the drug appears in the blood, urine, and stool after it is administered to healthy participants. Information about any side effects that may occur will also be collected. This study will last up to 22 days for each participant, not including screening. Screening is required within 28 days prior to enrollment

Start Date01 Sep 2014

Sponsor / Collaborator

Eli Lilly & Co.

NCT02194465

/ CompletedPhase 2

A Randomized, Placebo-Controlled, Double-Blinded, Parallel, Phase 2a Study to Evaluate the Safety and Efficacy of LY2623091 in Patients With Primary Hypertension

The main purpose of this study is to evaluate the safety and effectiveness of the study drug known as LY2623091 in participants with high blood pressure.

Start Date01 Aug 2014

Sponsor / Collaborator

Eli Lilly & Co.

100 Clinical Results associated with LY-2623091

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100 Translational Medicine associated with LY-2623091

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100 Patents (Medical) associated with LY-2623091

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6

Literatures (Medical) associated with LY-2623091

01 May 2021·Drug Development ResearchQ3 · MEDICINE

Role of mineralocorticoid receptor antagonists in kidney diseases

Q3 · MEDICINE

Review

Author: Joharapurkar, Amit ; Jain, Mukul ; Patel, Vishal

AbstractMineralocorticoid receptor (MR) antagonists, for example, spironolactone and eplerenone, are in clinical use to treat hypertension. Increasing evidence suggests that mineralocorticoid receptor activation causes the pathogenesis and progression of chronic kidney disease. Aldosterone‐induced MR activation increases inflammation, fibrosis, and oxidative stress in the kidney. MR antagonists (MRAs) have demonstrated therapeutic actions in chronic kidney disease (CKD), diabetic nephropathy (DN), renal fibrosis, and drug‐induced renal injury in preclinical and clinical studies. We have summarized and discussed these studies in this review. The nonsteroidal MRA, esaxerenone, recently received approval for the treatment of hypertension. It has also shown a positive therapeutic effect in phase 3 clinical trials in patients with DN. Other nonsteroidal MRA such as apararenone, finerenone, AZD9977, and LY2623091 are in different clinical trials in patients with hypertension suffering from renal or hepatic fibrotic diseases. Hyperkalemia associated with MRA therapy has frequently led to the discontinuation of the treatment. The new generation nonsteroidal MRAs like esaxerenone are less likely to cause hyperkalemia at therapeutic doses. It appears that the nonsteroidal MRAs can provide optimum therapeutic benefit for patients suffering from kidney diseases.

01 Jan 2020·European Journal of Medicinal ChemistryQ1 · MEDICINE

Structural attributes influencing unbound tissue distribution

Q1 · MEDICINE

Article

Author: Tess, David ; Di, Li ; Scott, Dennis ; Chang, George ; Kalgutkar, Amit S ; Orozco, Christine C ; Litchfield, John ; Filipski, Kevin J ; Riccardi, Keith ; Atkinson, Karen ; Ryu, Sangwoo ; Lin, Jian ; Mongillo, Robert K ; Keefer, Christopher

Unbound tissue-to-plasma partition coefficients (K_puu) were determined for 56 structurally diverse compounds in rats following intravenous infusion. Five tissues were included in the study: white adipose, brain, heart, liver, and skeletal muscle. The rank ordering of the median tissue K_puu values was: liver (4.5) > heart (1.8) > adipose (1.2) > skeletal muscle (0.6) > brain (0.05), with liver being most enriched and brain most impaired. The median K_puu values of acids and zwitterions were lower than those of bases and neutrals in all tissues but liver. Selective tissue distribution was observed, dependent upon chemotype, which demonstrated the feasibility of targeting or restricting drug exposure in certain tissues through rational design. Physicochemical attributes for K_puu were identified using recursive partitioning, which further classified compounds with enriched or impaired tissue distribution. The attributes identified provided valuable insight on design principles for asymmetric tissue distribution to improve efficacy or reduce toxicity.

01 Nov 2017·International Journal of Pharmacokinetics

Physiologically Based Pharmacokinetic Modeling to Understand the Observed Drug–Drug Interaction of LY2623091 with CYP3A Inhibitors Itraconazole and Diltiazem

Author: Dickinson, Gemma L ; Chaudhary, Archana ; Hall, Stephen D ; Phillips, Diane L ; Posada, Maria M

Aims: Drug–drug interaction studies were used to estimate CYP3A4-dependent clearance of LY2623091. Methods: in a cross-over design, healthy adults received a single 6-mg dose of LY2623091 at baseline. Itraconazole (200 mg twice on day 1 then daily × 19 days; n = 16) and diltiazem (240 mg Extended Release daily × 13 days; n = 16) were given. On days 6 and 4, respectively, LY2623091 was dosed 1 h after itraconazole/diltiazem. Pharmacokinetic samples were obtained and static and dynamic models were used to assess interaction. Results: Area under the concentration–time curve for LY2623091 increased 2.2-fold with itraconazole and 1.4-fold with diltiazem. Maximum plasma concentration did not change. The physiologically based pharmacokinetic model overpredicted itraconazole and hydroxy–itraconazole concentrations. Extraction by CYP3A4 was ∼0.5; gut wall extraction was negligible. Conclusion: Interaction risk requires early clinical assessment to quantify the candidate drug. (Clinical trial registration number: NCT02300259). Data deposition: deposition pending.

100 Deals associated with LY-2623091

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External Link

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB15367

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Essential Hypertension	Phase 2	Canada	Eli Lilly & Co.	01 Aug 2014
Essential Hypertension	Phase 2	United States	Eli Lilly & Co.	01 Aug 2014
Essential Hypertension	Phase 2	Puerto Rico	Eli Lilly & Co.	01 Aug 2014
Chronic Kidney Diseases	Phase 2	Bulgaria	Eli Lilly & Co.	01 Sep 2011
Chronic Kidney Diseases	Phase 2	South Africa	Eli Lilly & Co.	01 Sep 2011

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02194465 (CTgov)	Phase 2	Essential Hypertension	304	Placebo (Placebo)	fdxcsoipzs(ulpaiqluju) = kpuuwuqsrq uwvfqmkhxn (fljajrgllp, snkretgoym - ckzxbblzgb) View more	-	26 Jun 2020
				Placebo+LY2623091 (13 mg LY2623091)	fdxcsoipzs(ulpaiqluju) = tokcszdekw uwvfqmkhxn (fljajrgllp, kcddhukxzi - nuvdpmhubm) View more
NCT02300259 (CTgov)	Phase 1	-	48	LY2623091 (LY2623091 (Group 1))	tojlyczcje(ogkzpgghvp) = ubkixjkbgt hmsmugjjhi (owhhzfwdmk, immstwdtyy - tqpyccmfbr) View more	-	26 Jun 2020
				Itraconazole+LY2623091 (Itraconazole + LY2623091 (Group 1))	tojlyczcje(ogkzpgghvp) = tumxkitinw hmsmugjjhi (owhhzfwdmk, rpyawbpfmz - ehclcpcnzb) View more
NCT02242981 (CTgov)	Phase 1	-	6	LY2623091	kxtmnceulo(aaxfumpulw) = wwdtatsgml ybwuctqvzj (igrepisjnm, dcfbsigddt - iadcdqzefy) View more	-	26 Jun 2020