ZYBT1, a potent, irreversible Bruton's Tyrosine Kinase (BTK) inhibitor that inhibits the C481S BTK with profound efficacy against arthritis and cancer.

Bruton's tyrosine kinase (BTK) plays a central and pivotal role in controlling the pathways involved in the pathobiology of cancer, rheumatoid arthritis (RA), and other autoimmune disorders. ZYBT1 is a potent, irreversible, specific BTK inhibitor that inhibits the ibrutinib-resistant C481S BTK with nanomolar potency. ZYBT1 is found to be a promising molecule to treat both cancer and RA.

Lack of inhibition of CYP2C8 by saroglitazar magnesium: In vivo assessment using montelukast, rosiglitazone, pioglitazone, repaglinide and paclitaxel as victim drugs in Wistar rats.

Saroglitazar, a PPAR αҮ agonist, is currently undergoing global development for the treatment of NASH and other indications. Saroglitazar showed CYP2C8 inhibition in human liver microsomes (IC: 2.9 μM).

An approach to floating knee injury in Indian Population: An analysis of 52 patients.

Background: Floating knee is a condition resulting from high energy trauma usually associated with minor to life threatening injuries making it challanging to treat There are no studies available in literature describing cross leg sitting and squatting after surgical management of floating knee. This study analyzes prognostic factors, plan of management, functional outcomes (special attention to squatting and cross legged sitting), complications.

Materials And Methods: 52 patients with floating knee injuries treated over a period of 3 years were included in this study.

Assessment of the cytochrome P450 (CYP) inhibition potential of ZYTP1, a novel poly (ADP-ribose) polymerase inhibitor.

ZYTP1 is a novel Poly (ADP-ribose) polymerase protein inhibitor being developed for cancer indications. The focus of the work was to determine if ZYTP1 had a perpetrator role in the inhibition of cytochrome P450 (CYP) enzymes to aid dosing decisions during the clinical development of ZYTP1. ZYTP1 IC for CYP1A2, 2B6, 2C8, 2C9, 2C19, 2D6 and 3A4/5 was determined using human liver microsomes and LC-MS/MS detection.

Identification and preclinical characterization of a novel and potent poly (ADP-ribose) polymerase (PARP) inhibitor ZYTP1.

Purpose: Poly(ADP-ribose) polymerase-1 (PARP-1) is a nuclear enzyme involved in the detection and repair of DNA damage. Studies have shown that inhibition of PARP and Tankyrase (TNKS) has significant antitumor effect in several types of cancers including BRCA-negative breast cancers.

Methods: Identification of ZYTP1, a novel PARP inhibitor, through a battery of in vitro assays and in vivo studies.

Dual PPARα/γ agonist saroglitazar improves liver histopathology and biochemistry in experimental NASH models.

Background & Aims: Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are common clinico-pathological conditions that affect millions of patients worldwide. In this study, the efficacy of saroglitazar, a novel PPARα/γ agonist, was assessed in models of NAFLD/NASH.

Methods & Results: HepG2 cells treated with palmitic acid (PA;0.

A sensitive assay for ZYAN1 in human whole blood and urine utilizing positive LC-MS/MS electrospray ionization.

Aim: A sensitive LC-MS/MS method was developed and validated for estimation of ZYAN1 in human blood/urine.

Methods: An analog internal standard IOX2 along with ZYAN1 was quantified using selective reaction monitoring in positive mode. The chromatographic separation was performed by gradient elution with C analytical column (3 µm, 50 mm × 2.

ZY15557, a novel, long acting inhibitor of dipeptidyl peptidase-4, for the treatment of Type 2 diabetes mellitus.

Background And Purpose: Dipeptidyl peptidase (DPP)-4 inhibitors increase levels of glucagon-like peptide-1 (GLP-1) and provide clinical benefit in the treatment of type 2 diabetes mellitus. As longer acting inhibitors have therapeutic advantages, we developed a novel DPP-4 inhibitor, ZY15557, that has a sustained action and long half-life.

Experimental Approach: We studied the potency, selectivity, efficacy and duration of action of ZY15557, in vitro, with assays of DPP-4 activity.

Sensitive and specific LC-ESI-MS/MS method for determination of ZYDPLA1, a novel long-acting dipeptidyl peptidase 4 inhibitor in rat plasma: An application for toxicokinetic study in rats.

A rapid and highly specific assay was developed and validated for the estimation of ZYDPLA1 in rat plasma using liquid chromatography coupled to tandem mass spectrometry with positive electrospray ionization. Method validation comprised of parameters such as specificity, matrix effect, precision, accuracy, recovery, stability, etc. The assay procedure involved a simple protein precipitation of ZYDPLA1 and alprazolam (internal standard) from rat plasma using acetonitrile.

HPV vaccines: Global perspectives.

The discovery of HPV as the etiological factor for HPV-associated malignancies and disease has opened up several opportunities for prevention and therapy. Current commercially available HPV vaccines (Gardasil, Gardasil 9, and Cervarix) are prophylactic in nature and derived from adjuvanted L1-based virus-like particles of HPV. Globally, through several clinical trials, they were found to be very safe and efficacious.

Is the Inhibition of Dipeptidyl Peptidase-4 (DDP-4) Enzyme Route Dependent and/or Driven by High Peak Concentration?- Seeking Answers with ZYDPLA1, a Novel Long Acting DPP-4 Inhibitor, in a Rodent Model.

ZYDPLA1 is a long acting enzyme dipeptidyl peptidase-4 (DPP-4) inhibitor. The comparative effect of DPP-4 inhibition after intravenous (IV) and oral administration of ZYDPLA1 in a rat model was evaluated to answer the question of route dependency and/or the need of high plasma levels of ZYDPLA1. The study was conducted using parallel design in male Wistar rats for IV/oral route (n=9 and 6, for IV and oral respectively).

Antiepileptic Drugs-induced Stevens-Johnson syndrome: A case Series.

Stevens-Johnson syndrome (SJS) is an acute life-threatening mucocutaneous reaction, characterized by extensive necrosis and detachment of the epidermis from the skin. The overall incidence of SJS is seen in five cases per million people per year. SJS is typically caused by drugs and is a kind of idiosyncratic reaction.

Changes in Capacity and Performance in Mobility Across Different Environmental Settings in Children with Cerebral Palsy: An Exploratory Study.

Background: Children with cerebral palsy, although having similar diagnosis, varies in their abilities & level of functioning within & across different environmental context e.g. home, school or community setting.

Saroglitazar, a novel PPARα/γ agonist with predominant PPARα activity, shows lipid-lowering and insulin-sensitizing effects in preclinical models.

Saroglitazar is a novel nonthiazolidinediones (TZD) and nonfibric acid derivative designed to act as dual regulator of lipids and glucose metabolism by activating peroxisome proliferator-activated receptors (PPAR). These studies evaluate the efficacy and safety profile of Saroglitazar in preclinical in vitro and in vivo models. The EC50 values of Saroglitazar assessed in HepG2 cells using PPAR transactivation assay for hPPARα and hPPARγ were 0.

Pharmacological characterization of ZYDPLA1, a novel long-acting dipeptidyl peptidase-4 inhibitor.

Objective: Dipeptidyl peptidase-4 (DPP-4) is responsible for degradation of glucagon-like peptide 1 (GLP-1) and gastric inhibitory polypeptide (GIP), the endogenous incretins that stimulate glucose-dependent insulin secretion. The objective was to evaluate preclinical profile of a novel DPP-4 inhibitor ZYDPLA1.

Methods: In vitro inhibition potency and selectivity were assessed using recombinant enzymes and/or plasma.

Results of posterior dislocation of elbow associated with bony and soft tissue injury.

Unlabelled: Elbow trauma is challenging to manage by virtue of its complex articular structure and capsuloligamentous and musculotendinous arrangements. We included 17 patients with elbow dislocation and associated injuries in this study. The study protocol included early elbow reduction and planned fixation of the medial or lateral condyle, coronoid and radial head.

HPLC-FLD for the simultaneous determination of primary and secondary amino acids from complex biological sample by pre-column derivatization.

A rapid, sensitive, and reproducible pre-column derivatisation procedure has been established for the simultaneous determination of 20 amino acids by high-performance liquid chromatography using fluorescence detection. The amino acids were derivatized using o-phthalaldehyde and 9-fluorenylmethyl-chloroformate reagents. The optimal conditions for simultaneous separation and detection of both primary and secondary amino acids were investigated.

Magnetic resonance myelography in early postoperative lumbar discectomy: An efficient and cost effective modality.

Background: Magnetic resonance myelography (MRM) after lumbar discectomy is all too often an unrewarding challenge. A constellation of findings are inevitable, and determining their significance is often difficult. MRM is a noninvasive technique that can provide anatomical information about the subarachnoid space.

Involvement of adipokines in rimonabant-mediated insulin sensitivity in ob/ob mice.

Objectives: It has been recently reported that blockade of type 1 cannabinoid (CB1) receptors by specific antagonists or genetic manipulation alleviates dyslipidaemia, hyperglycaemia and insulin resistance in animal models of obesity and type 2 diabetes. However, the precise role of adipokines in the insulin-sensitising effects of the CB1 antagonist rimonabant is not clear.

Methods: ob/ob mice were treated with different doses of rimonabant and then subjected to an oral glucose tolerance test.

Subtherapeutic dose of pioglitazone reduces expression of inflammatory adipokines in db/db mice.

Agonists of the thiazolidinedione class of peroxisome proliferator-activated receptor-gamma exhibit both insulin-sensitizing and anti-inflammatory effects. We hypothesized that pioglitazone might be able to exert its anti-inflammatory properties at a lower dose than that required for its insulin-sensitizing effect. In order to investigate this hypothesis, we evaluated the effects of pioglitazone on inflammatory as well as metabolic biomarkers in serum and white adipose tissue (WAT) at 2 different doses.

Hair growth stimulator property of thienyl substituted pyrazole carboxamide derivatives as a CB1 receptor antagonist with in vivo antiobesity effect.

A few thienyl substituted pyrazole derivatives were synthesized to aid in the characterization of the cannabinoid receptor antagonist and also to serve as potentially useful antiobesity agent. Structural requirements for selective CB1 receptor antagonistic activity of 5-thienyl pyrazole derivatives included the structural similarity with potent, specific antagonist rimonabant 1. Compound 3 has been identified as a hair growth stimulator and an antiobesity agent in animal models.

Antithrombotic effects due to pharmacological modulation of thrombin-activatable fibrinolysis inhibitor in rats.

Thrombin-activatable fibrinolysis inhibitor (TAFI) is a basic carboxypeptidase zymogen that can be activated by thrombin. Activated TAFI (TAFIa) cleaves carboxyl-terminal lysine residues from partially degraded fibrin, rendering it resistant to fibrinolysis by endogenous tissue plasminogen activator (tPA). Carboxypeptidase inhibitor (CPI) isolated from potato inhibits TAFIa and reduces clot lysis time in rabbit and mouse plasma.

Facile synthesis, ex-vivo and in vitro screening of 3-sulfonamide derivative of 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxylic acid piperidin-1-ylamide (SR141716) a potent CB1 receptor antagonist.

Facile synthesis of biaryl pyrazole sulfonamide derivative of 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxylic acid piperidin-1-ylamide (SR141716, 1) and an investigation of the effect of replacement of the -CO group in the compound 1 by the -SO(2) group in the aminopiperidine region is reported. Primary ex-vivo pharmacological testing and in vitro screening of sulfonamide derivative 2 showed the loss of CB1 receptor antagonism.