Discoidin domain receptor inhibitors as anticancer agents: A systematic review on recent development of DDRs inhibitors, their resistance and structure activity relationship

Shenoy, Ganesh Prasad; Pal, Rohit; Swamy, P.M. Gurubasavaraja; Singh, Ekta; Raghavendra, Narasimha; Dhiwar, Prasad Sanjay

doi:10.1016/j.bioorg.2022.106215

Cited by 15 publications

(7 citation statements)

References 109 publications

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“…A cell cycle analysis showed that arrest of the cell cycle of A549 cells occurred at the S phase in derivative 7 and the G1 phase in derivative 8 [27] (Figure 4). Moreover, a new family of 3,4-dihydro-2H- [1,4]oxazino [2,3-f]quinazoline derivatives that target EGFR was described by Qin et al (Figure 5) [28]. With an IC50 ≤ 937.7 nM, the synthesized candidates showed strong EGFR inhibitory efficacy.…”

Section: Epidermal Growth Factor Receptor (Egfr) Inhibitorsmentioning

confidence: 99%

“…The fast growth of abnormal cells that eventually spread to other organs after initially residing in one area is one of the primary characteristics of cancer. This phenomenon is known as metastasis [ 4 ]. Widespread metastases are the main reason behind cancer-related deaths [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

“…This phenomenon is known as metastasis [ 4 ]. Widespread metastases are the main reason behind cancer-related deaths [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

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Recent Advances in Structural Optimization of Quinazoline-Based Protein Kinase Inhibitors for Cancer Therapy (2021–Present)

Abdel-Mohsen,

Anwar,

Ahmed

et al. 2024

Molecules

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Cancer is a complicated, multifaceted disease that can impact any organ in the body. Various chemotherapeutic agents have a low selectivity and are very toxic when used alone or in combination with others. Resistance is one of the most important hurdles that develop due to the use of many anticancer therapeutics. As a result, treating cancer requires a target-specific palliative care strategy. Remarkable scientific discoveries have shed light on several of the molecular mechanisms underlying cancer, resulting in the development of various targeted anticancer agents. One of the most important heterocyclic motifs is quinazoline, which has a wide range of biological uses and chemical reactivities. Newer, more sophisticated medications with quinazoline structures have been found in the last few years, and great strides have been made in creating effective protocols for building these pharmacologically active scaffolds. A new class of chemotherapeutic agents known as quinazoline-based derivatives possessing anticancer properties consists of several well-known compounds that block different protein kinases and other molecular targets. This review highlights recent updates (2021–2024) on various quinazoline-based derivatives acting against different protein kinases as anticancer chemotherapeutics. It also provides guidance for the design and synthesis of novel quinazoline analogues that could serve as lead compounds.

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Section: Epidermal Growth Factor Receptor (Egfr) Inhibitorsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Recent Advances in Structural Optimization of Quinazoline-Based Protein Kinase Inhibitors for Cancer Therapy (2021–Present)

Abdel-Mohsen,

Anwar,

Ahmed

et al. 2024

Molecules

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“…Nilotinib has been shown to block the association of myosin IIA with the DDR1 kinase domain to reduce tractional collagen contraction in vitro ( Figure 4 ) ( 21 ). Other potent lead compounds for inhibiting selectively DDRs include compounds 13-21 ( 98 ). Among them, compounds 13, 18, and 21 are representative of 1, 2, 3, 4-tetrahydroisoquinoline derivatives, pyrazole fused pyrimidine derivatives, and indazole derivatives against DDR1, respectively; compounds 14-16, compound 17, and compound 19 separately belong to di-amide derivatives, dasatinib analogs and indole analogs against DDR1 and DDR2; and the compound 20 derives from pyridine derivatives against DDR2 ( 98 ).…”

Section: Ddr Inhibitorsmentioning

confidence: 99%

“…Other potent lead compounds for inhibiting selectively DDRs include compounds 13-21 ( 98 ). Among them, compounds 13, 18, and 21 are representative of 1, 2, 3, 4-tetrahydroisoquinoline derivatives, pyrazole fused pyrimidine derivatives, and indazole derivatives against DDR1, respectively; compounds 14-16, compound 17, and compound 19 separately belong to di-amide derivatives, dasatinib analogs and indole analogs against DDR1 and DDR2; and the compound 20 derives from pyridine derivatives against DDR2 ( 98 ). Currently, several clinical trials have been conducted with drugs such as dasatinib, nilotinib, and sitravatinib for different cancers, including squamous cell lung carcinoma, advanced or refractory lymphoma, advanced solid malignancies, hematopoietic neoplasm, etc ( 99 – 104 ).…”

Section: Ddr Inhibitorsmentioning

confidence: 99%

Focusing on discoidin domain receptors in premalignant and malignant liver diseases

Gong

Xu²,

Zhang³

2023

Front. Oncol.

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Discoidin domain receptors (DDRs) are receptor tyrosine kinases on the membrane surface that bind to extracellular collagens, but they are rarely expressed in normal liver tissues. Recent studies have demonstrated that DDRs participate in and influence the processes underlying premalignant and malignant liver diseases. A brief overview of the potential roles of DDR1 and DDR2 in premalignant and malignant liver diseases is presented. DDR1 has proinflammatory and profibrotic benefits and promotes the invasion, migration and liver metastasis of tumour cells. However, DDR2 may play a pathogenic role in early-stage liver injury (prefibrotic stage) and a different role in chronic liver fibrosis and in metastatic liver cancer. These views are critically significant and first described in detail in this review. The main purpose of this review was to describe how DDRs act in premalignant and malignant liver diseases and their potential mechanisms through an in-depth summary of preclinical in vitro and in vivo studies. Our work aims to provide new ideas for cancer treatment and accelerate translation from bench to bedside.

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Advancement of DDR1 and DDR2 Inhibitors: Therapeutic Potential of Bioactive Compounds, Designing Strategies, and Structure‐Activity Relationship (SAR)

Pal,

Kumaraswamy,

Md. Ashadul

et al. 2024

ChemistrySelect

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DDR1 and DDR2 are nonintegrin collagen receptors in the receptor tyrosine kinase family. Both DDRs bind to various collagen types and perform crucial functions in embryo development. DDRs are different from other receptor tyrosine kinases due to their interaction with extracellular matrix components and unusual activation kinetics. DDR regulates cell migration, survival, proliferation, differentiation, and extracellular matrix remodeling. Dysregulated DDR function is linked to the advancement of several human illnesses, including fibrosis, arthritis, neurodegenerative diseases, and cancer. DDRs play a vital role in disease progression and development. Therefore, the use of DDR inhibitors represents a promising therapeutic strategy, particularly for disorders with limited therapy alternatives. In recent years, DDRs have been regarded as attractive targets for drug development, as evidenced by a significant rise in research in this field. The current review illustrates about recent advancement of small molecules, their designing strategies and structure‐activity relationship. The DDR inhibitors can contain various core structures such as pyrimidine, phthalazine, pyrazole, pyrazine, imidazo[1,2‐a]sspyrazine, quinazoline, and thieno[3,2‐b]pyridin‐7‐yl derivatives. Furthermore, based on the constructive analysis of the published derivatives, we found that the majority of the powerful compounds have a similar scaffold (amide linker, hydrophobic tail, hinge binder with or without spacer). Among the different literature, the most potent compounds 4 (imidazo[1,2‐a]pyrazine), 5 (pyridine), 19 (pyridine), and 24 (quinazoline) displayed potent activity against DDR1 with IC50 values ranging from 2.26 – 4.67 nM, while DDR2 IC50 values ranging from 3.2 – 7.29 nM. This approach will help medicinal chemists to refine and develop novel small molecules targeting DDR1 and DDR2.

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Discoidin domain receptor inhibitors as anticancer agents: A systematic review on recent development of DDRs inhibitors, their resistance and structure activity relationship

Cited by 15 publications

References 109 publications

Recent Advances in Structural Optimization of Quinazoline-Based Protein Kinase Inhibitors for Cancer Therapy (2021–Present)

Recent Advances in Structural Optimization of Quinazoline-Based Protein Kinase Inhibitors for Cancer Therapy (2021–Present)

Focusing on discoidin domain receptors in premalignant and malignant liver diseases

Advancement of DDR1 and DDR2 Inhibitors: Therapeutic Potential of Bioactive Compounds, Designing Strategies, and Structure‐Activity Relationship (SAR)

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