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Overview

Tags

Neoplasms

Digestive System Disorders

Respiratory Diseases

siRNA

Small molecule drug

Proteolysis-targeting chimeras (PROTAC)

Disease domain score

A glimpse into the focused therapeutic areas

Technology Platform

Most used technologies in drug development

Targets

Most frequently developed targets

Disease Domain	Count

Neoplasms	9
Endocrinology and Metabolic Disease	2
Hemic and Lymphatic Diseases	1

Top 5 Drug Type	Count

siRNA	4
Small molecule drug	3
Proteolysis-targeting chimeras (PROTAC)	2

Top 5 Target	Count

ERα(Estrogen receptor alpha)	2
BTK(Tyrosine-protein kinase BTK)	1
PMVK(phosphomevalonate kinase)	1
HPV E6 x HPV E7	1
SERT(Serotonin transporter)	1

AbstractBackground: High-risk human papillomavirus (HPV) type 16 is the major etiological agent found in more than 60% of patients with cervical cancer and associated with cancer development and progression. Persistent expression HPV E6 and E7 oncoproteins are essential for the initiation and maintenance of cervical cancer. The therapeutic approaches targeting HPV E6 and E7 have been proved to be highly efficient in killing malignant cells. The suppression of HPV 16 E6/E7 expression by the short interfering RNA (siRNA) was more effective in combination therapy with cisplatin (CDDP) for cervical cancer. ENB101-LNP is an ionizable lipid nanoparticles (LNPs) encapsulating siRNA against E6/E7 of HPV 16 for delivery to the tumor cells.Methods: To investigate the anticancer efficacy and mechanism of ENB101-LNP combined with cisplatin in cervical cancer; the xenograft model was generated by the injection of CaSki cells subcutaneously into BALB/c nude mice. Mice were randomly divided into six groups: 1) blank control; 2) 1mg/kg ENB101-LNP; 3) 3mg/kg ENB101-LNP; 4) CDDP; 5) 1mg/kg ENB101-LNP-CDDP; 6) 3mg/kg ENB101-LNP-CDDP. ENB101-LNP was treated with intravenous injection three times weekly for 3 weeks and CDDP was treated with IP injection once a week for 3 weeks. Tumor growth curves were plotted to calculate the tumor inhibition rate. Mice were sacrificed one week after the last treatment and the tumor tissues were investigated using histopathology, immunohistochemical staining and western blotting.Results: Compared with the control and the other treatment groups, the tumor growth was significantly inhibited (P < 0.05). The tumor inhibition rate was 29.7% in 1mg/kg ENB101-LNP group, 29.6% in 3mg/kg ENB101-LNP group, 34.0% in CDDP group, 47.0% in 1mg/kg ENB101-LNP-CDDP group. At the dose of 3mg ENB101-LNP/kg combined with CDDP exhibited superior antitumor efficacy, the tumor inhibition rate was 68.8%. The successful ENB101-LNP mediated knockdown (with up to 80%) of HPV16 E6/E7 in tumors of both 1mg/kg and 3mg/kg groups was confirmed by RT-PCR. The ENB101-LNP increased p53 and p21 expression in tumors compared to control and CDDP alone groups and combination treatment with CDDP showed decreased expression of PD-L1 expression compared to CDDP alone group. The treatment of ENB101-LNP and combination with CDDP showed significant increase in apoptotic cells compared to control and single-agent groups respectively.Conclusions: The ENB101-LNP inhibiting E6 and E7 of HPV 16 in combination with CDDP showed promising anticancer activity in the cervical cancer cells xenograft mouse model.Citation Format: Sung Wan Kang, Shin-Wha Lee, Ji-young Lee, Ok Ju Kang, Hyejeong Kim, Yisak Kim, Yong-Man Kim. Evaluation of anti-cancer efficacy of lipid nanoparticles containing siRNA against HPV16 E6 and E7 combined with cisplatin in xenograft model of cervical cancer. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3779.

PharmaceuticalsQ3 · MEDICINE

Fulvestrant-3-Boronic Acid (ZB716) Demonstrates Oral Bioavailability and Favorable Pharmacokinetic Profile in Preclinical ADME Studies

Q3 · MEDICINE

ArticleOA

Author: Rajasekaran, Nirmal ; Guo, Shanchun ; Kang, Borui ; Hossain, Ahamed ; Liu, Jiawang ; Jung, Hunsoon ; Wang, Guangdi ; Kim, Hongjoong ; Zhang, Changde

Fulvestrant-3-boronic acid (ZB716), an oral selective estrogen receptor degrader (SERD) under clinical development, has been investigated in ADME studies to characterize its absorption, metabolism, and pharmacokinetics. ZB716 was found to have high plasma protein binding in human and animal plasma, and low intestinal mucosal permeability. ZB716 had high clearance in hepatocytes of all species tested. ZB716 was metabolized primarily by CYP2D6 and CYP3A. In human liver microsomes, ZB716 demonstrated relatively low inhibition of CYP1A2, 2C8, 2C9, 2C19, 2D6, and 3A4 (when testosterone was used as the substrate), and no inhibition of CYP2B6 and 3A4 (when midazolam was used as the substrate). In assays for enzyme activity, ZB716 induced CYP1A2, 2B6, and 3A4 in a concentration-dependent manner. Single-dose and repeated-dose pharmacokinetic studies in rats and dogs showed oral bioavailability, dose-proportional drug exposure, and drug accumulation as measured by maximum concentration and area under the concentration–time curve (AUC).

Frontiers in Oncology

Corrigendum: Dysregulation of miR-375/AEG-1 Axis by Human Papillomavirus 16/18-E6/E7 Promotes Cellular Proliferation, Migration, and Invasion in Cervical Cancer

Author: Shin, Young Kee ; Jung, Hun Soon ; Jayamohan, Sridharan ; Rajasekaran, Nirmal ; Arockiam, Antony Joseph Velanganni ; Kannan, Maheshkumar ; Moorthy, Rajesh Kannan

[This corrects the article DOI: 10.3389/fonc.2019.00847.].

100 Deals associated with EnhancedBio, Inc.

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100 Translational Medicine associated with EnhancedBio, Inc.

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Pipeline

Pipeline Snapshot as of 07 Nov 2024

The statistics for drugs in the Pipeline is the current organization and its subsidiaries are counted as organizations,Early Phase 1 is incorporated into Phase 1, Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3

Preclinical

8

1

Phase 2 Clinical

Other

1

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Current Projects

Drug(Targets)	Indications	Global Highest Phase

Borestrant ( ERα )	ER-positive/HER2-negative Breast Cancer More	Phase 2 Clinical
Mevisiran	Pancreatic Carcinoma More	Preclinical
Carvisiran	Head and Neck Neoplasms More	Preclinical
Corpitenib	Metastatic Colorectal Carcinoma More	Preclinical
ER-PROTAC(EnhancedBio, Inc.) ( ERα )	ER-positive/HER2-negative Breast Cancer More	Preclinical