Delving into the Latest Updates on Kanglaite with Synapse

Overview

Basic Info

Drug Type

Herbal medicine

Synonyms

KLT, KLTc, KLTi

+ [2]

Target-

Action

stimulants, inhibitors

Mechanism

Apoptosis stimulants, Cell cycle inhibitors

Therapeutic Areas

NeoplasmsDigestive System DisordersRespiratory Diseases+ [1]

Active Indication

NeoplasmsCachexiaLiver Cancer+ [1]

Inactive Indication

Advanced Lung Non-Small Cell Carcinomametastatic non-small cell lung cancerPancreatic Cancer+ [1]

Originator Organization

Zhejiang Kanglaite Pharmaceutical Co., Ltd.

Active Organization

Zhejiang Kanglaite Pharmaceutical Co., Ltd.

Inactive Organization

Kanglaite USA, Inc.

Drug Highest PhaseApproved

First Approval Date

China (01 Jan 1997),

Liver CancerNon-Small Cell Lung Cancer

Regulation-

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Kanglaite, a compound predominantly composed of polyunsaturated fatty acids (PUFAs), has been employed in the clinical treatment of adenocarcinoma non-small cell lung cancer (NSCLC) in China for decades. However, its therapeutic efficacy and specific mechanism in the treatment of squamous NSCLC remains unexplored. In this study, we demonstrate that the co-treatment with ferric ion significantly enhances the cytotoxic effects of kanglaite by inducing ferroptosis in NCL-H1703, a cell line of human lung squamous cell carcinoma. Mechanistic investigations reveal that kanglaite induces mitochondrial dysfunction resulting in reactive oxygen species (ROS) excessive production, which is critical for the induction of ferroptosis. Further analysis shows that kanglaite suppresses the PI3K/AKT signaling pathway, leading to increased IP3 generation. IP3 subsequently binds to and activates IP3R, an endoplasmic reticulum (ER) calcium channel, exacerbating the excessive calcium transfer from the ER to mitochondria. The overloaded mitochondrial calcium contributes to its dysfunction and elevates ROS production. To optimize the synergistic effects of ferric ion and kanglaite, we develop a mesoporous silica-based nanodrug delivery system co-loaded with Kanglaite and Fe₃O₄, which offers several notable advantages, including reduced drug dosage and a faster therapeutic onset. Finally, in an NCL-H1703 xenograft model, the DMSN/Fe₃O₄-Kanglaite nanodrug significantly inhibited tumor growth. In conclusion, we identified the function and mechanism of kanglaite in treatment of squamous NSCLC and have developed a DMSN/Fe₃O₄-Kanglaite nanodrug, providing a superior therapeutic approach for the treatment of squamous NSCLC.

01 Jan 2025·Phytomedicine

Autocrine and paracrine LIF signals to collaborate sorafenib-resistance in hepatocellular carcinoma and effects of Kanglaite Injection

Article

Author: Wang, Yu ; Pu, Weiling ; Yin, Shuangshuang ; Shao, Yingying ; Han, Lifeng ; Yu, Haiyang ; Su, Ranran ; Zhong, Hao

BACKGROUNDSorafenib (SFN) is the first-line medicine for advanced hepatocellular carcinoma (HCC). However, Sorafenib resistance is a main challenge of therapeutic efficacy, and the mechanisms have not been fully clarified.PURPOSEThe purpose of this study was to investigate the therapeutic potential and mechanism of action of LIF in modulating the microenvironment of SFN resistance as well as Kanglaite Injection (KLTI) in ameliorating SFN resistance in HCC and to guide future research directions for drug combination for HCC.METHODSEstablished SFN-resistance HCC cell line was used to study the relationship between resistance and immunosuppression in HCC-tumor microenvironment (TME). In vivo macrophage and natural killer (NK) cells depletion were achieved by clodronate liposomes (CL) and anti-NK1.1. In vitro multiple cell co-culture systems were used to determine the effects of KLTI on SFN-resistant. Likewise, flow cytometry, qRT-PCR, Western blot, and immunohistochemistry analysis were performed for further mechanistic investigation.RESULTSTumor associated-macrophages (TAMs) and NK cells mediated SFN-resistance in murine HCC. In the case of SFN resistance, the paracrine-leukemia inhibitory factor (LIF) by M2-like TAMs increased and potently suppressed NK cells proliferation and cytotoxicity, which finally inducing NK cells exhaustion and malignancy of HCC metastasis. Meanwhile, SFN resistance led to the increased autocrine-LIF of tumor cells, and further promoted the protective autophagy and activation of the acquired drug-resistant pathway PI3K/Akt/mTOR. KLTI could ameliorate the resistance of tumor immune microenvironment (TIME) and enhance the sensitivity of HCC to SFN by regulating LIF and macrophage-NK cell interaction.CONCLUSIONSOur findings verify the therapeutic effects of targeting LIF in SFN-resistance, uncover the potential mechanism for the increased sensitivity to SFN and sought to elucidate how this intervention might contribute to overcoming SFN resistance. KLTI is a promising immunomodulatory drug by regulating LIF and macrophage-NK cell interaction, which could be a potential combination partner for HCC treatment.

31 Dec 2024·Pharmaceutical Biology

Comparative efficacy and safety of Chinese medicine injections as an adjunctive therapy for cervical cancer in Chinese patients: a network meta-analysis

Review

Author: Zhang, Hongxing ; Wang, Qun ; Song, Haiyan ; Ma, Fei ; Wang, Zihong ; Zhang, Di ; Liu, Xianghong ; Xie, Hui ; Sun, Shiguang

CONTEXTChinese medicine injections (CMIs) are widely used as adjuvant therapy for cervical cancer in China. However, the effectiveness of different types of CMIs remains uncertain.OBJECTIVETo assess the effectiveness and safety of CMIs when used in conjunction with radiotherapy (RT) or concurrent chemoradiotherapy (CCRT), particularly in combination with cisplatin (DDP), docetaxel plus cisplatin (DP), and paclitaxel plus cisplatin (TP).MATERIALS AND METHODSRandomized controlled trials (RCTs) were searched in databases including CNKI, WanFang, VIP, SinoMed, PubMed, Cochrane Library, Embase, and Web of Science from inception to September 2023. We calculated the risk ratio with a 95% confidence interval and the surface under the cumulative ranking area curve (SUCRA) for the clinical efficacy rate (CER), the efficacy rate by Karnofsky Performance Status (KPS), and the rates of leukopenia reduction (LRR) and gastrointestinal reactions (GRR).RESULTSForty-seven RCTs were included, including nine CMI types: Aidi, Fufangkushen, Huangqi, Kangai (KA), Kanglaite (KLT), Renshenduotang, Shenqifuzheng (SQFZ), Shenmai (SM), and Yadanzi. KLT and KA were likely optimal choices with radiotherapy for CER and KPS, respectively. KA and KLT were optimal choices with RT + DDP for CER and GRR, respectively. KLT was the likely optimal choice with RT + DP for CER and KA for both KPS and GRR. SM and SQFZ were the likely optimal choices with RT + TP for CER and LRR, respectively.CONCLUSIONSThe optimal recommendation depends on whether CMIs are used with radiotherapy or concurrent chemoradiotherapy. More high-quality RCTs are needed to confirm further and update the existing evidence.

100 Deals associated with Kanglaite

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External Link

KEGG	Wiki	ATC	Drug Bank
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R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Neoplasms	China	Zhejiang Kanglaite Pharmaceutical Co., Ltd.	29 Dec 1997
Cachexia	China	Zhejiang Kanglaite Pharmaceutical Co., Ltd.	16 Dec 1997
Liver Cancer	China	Zhejiang Kanglaite Pharmaceutical Co., Ltd.	01 Jan 1997
Non-Small Cell Lung Cancer	China	Zhejiang Kanglaite Pharmaceutical Co., Ltd.	01 Jan 1997

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Advanced Lung Non-Small Cell Carcinoma	Phase 3	United States	Kanglaite USA, Inc.	01 May 2012
metastatic non-small cell lung cancer	Phase 3	United States	Kanglaite USA, Inc.	01 May 2012
Prostatic Cancer	Phase 3	United States	Kanglaite USA, Inc.	01 Nov 2011
Pancreatic Cancer	Discovery	United States	Kanglaite USA, Inc.	01 Aug 2008

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03101514 (CTgov)	Phase 2	Head and Neck Neoplasms	53	chemotherapy+Kanglaite	(sqqojcnldp) = wdjmyvukvz kcllcfckrb (pzjveivliq, gtwjwtazss - rvrayodwdz) View more	-	23 Jun 2021
NCT00733850 (ASCO2013)	Phase 2	Pancreatic Cancer	85	KLTi 30g/day plus gemcitabine	(jcptueigbh) = xipkfqlehb dadyxedhca (rnbtkjqdxr ) View more	-	20 May 2013
NCT00733850 (ASCO2013)	Phase 2	Pancreatic Cancer	85	Gemcitabine only	(jcptueigbh) = eizklywewa dadyxedhca (rnbtkjqdxr ) View more	-	20 May 2013
ASCO2011	Phase 2	Metastatic Pancreatic Cancer	58	Kanglaite Injection (KLT) + Gemcitabine hydrochloride (GEM)	(zwsncnizot) = upcbpadmue hlaldrbbjb (vwdqihqcol )	Positive	20 May 2011