Drug Information
Drug (ID: DG01260) and It's Reported Resistant Information
| Name |
YN-968D1
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| Synonyms |
Apatinib; Apatinib Mesylate; 1218779-75-9; Rivoceranib mesylate; YN968D1; YN-968D1; UNII-TK02X14ASJ; YN 968D1; TK02X14ASJ; N-(4-(1-Cyanocyclopentyl)phenyl)-2-((pyridin-4-ylmethyl)amino)nicotinamide Mesylate; 3-Pyridinecarboxamide, N-(4-(1-cyanocyclopentyl)phenyl)-2-((4-pyridinylmethyl)amino)-, methanesulfonate (1:1); N-[4-(1-cyanocyclopentyl)phenyl]-2-(pyridin-4-ylmethylamino)pyridine-3-carboxamide;methanesulfonic acid; Apatinib mesylate; 3-Pyridinecarboxamide, N-[4-(1-cyanocyclopentyl)phenyl]-2-[(4-pyridinylmethyl)amino]-, methanesulfonate (1:1); Alitan (TN); Apatinib-YN968D1; Apatinib - YN968D1; Rivoceranib mesylate (USAN); MLS006011286; CHEMBL3545414; SCHEMBL21847695; DTXSID80153427; HMS3655H12; AOB87128; BCP15234; Apatinib (registered name in China); BDBM50152828; s2221; AKOS026750547; BCP9000308; CCG-269641; CS-0694; SB16589; N-(4-(1-cyanocyclopentyl)phenyl)-2-((pyridin-4-ylmethyl)amino)nicotinamide methanesulfonate; HY-13342; SMR004703036; SW220296-1; D11289; N-(4-(1-cyanocyclopentyl)phenyl)-2-(pyridin-4-ylmethylamino)nicotinamide mesylate; N-[4-(1-cyanocyclopentyl)phenyl]-2-(4-pyridylmethyl)amino-3-pyridine carboxyamide mesylate; N-(4-(1-cyanocyclopentyl)phenyl)-2-((pyridin-4-ylmethyl)amino)pyridine-3-carboxamide mesylate
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| Indication |
In total 1 Indication(s)
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| Structure |
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| Drug Resistance Disease(s) |
Disease(s) with Clinically Reported Resistance for This Drug
(1 diseases)
Thyroid cancer [ICD-11: 2D10]
[1]
Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug
(1 diseases)
Lung cancer [ICD-11: 2C25]
[2]
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| Target | Vascular endothelial growth factor receptor 2 (KDR) | VGFR2_HUMAN | [1] | ||
| Click to Show/Hide the Molecular Information and External Link(s) of This Drug | |||||
| Formula |
C25H27N5O4S
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| IsoSMILES |
CS(=O)(=O)O.C1CCC(C1)(C#N)C2=CC=C(C=C2)NC(=O)C3=C(N=CC=C3)NCC4=CC=NC=C4
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| InChI |
1S/C24H23N5O.CH4O3S/c25-17-24(11-1-2-12-24)19-5-7-20(8-6-19)29-23(30)21-4-3-13-27-22(21)28-16-18-9-14-26-15-10-18;1-5(2,3)4/h3-10,13-15H,1-2,11-12,16H2,(H,27,28)(H,29,30);1H3,(H,2,3,4)
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| InChIKey |
FYJROXRIVQPKRY-UHFFFAOYSA-N
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| PubChem CID | |||||
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Type(s) of Resistant Mechanism of This Drug
MRAP: Metabolic Reprogramming via Altered Pathways
UAPP: Unusual Activation of Pro-survival Pathway
Drug Resistance Data Categorized by Their Corresponding Diseases
ICD-02: Benign/in-situ/malignant neoplasm
Lung cancer [ICD-11: 2C25]
| Drug Resistance Data Categorized by Their Corresponding Mechanisms | ||||
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Metabolic Reprogramming via Altered Pathways (MRAP)
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| Key Molecule: Activating transcription factor 4 (ATF4) | [2] | |||
| Metabolic Type | Glutamine metabolism | |||
| Resistant Disease | Non-small cell lung carcinoma [ICD-11: 2C25.Y] | |||
| Molecule Alteration | Expression | Up-regulation |
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| Experimental Note | Revealed Based on the Cell Line Data | |||
| In Vitro Model | A549 cells | Lung | Homo sapiens (Human) | CVCL_0023 |
| H460 cells | Lung | Homo sapiens (Human) | CVCL_0459 | |
| Experiment for Molecule Alteration |
qRT-PCR; Western blot analysis | |||
| Experiment for Drug Resistance |
Cell viability assay | |||
| Mechanism Description | Apatinib repressed the expression of GLS1, the initial and rate-limiting enzyme of glutamine catabolism. However, the broken metabolic balance led to the activation of the amino acid response (AAR) pathway, known as the GCN2/eIF2alpha/ATF4 pathway. Moreover, activation of ATF4 was responsible for the induction of SLC1A5 and ASNS, which promoted the consumption and metabolization of glutamine. Interestingly, the combination of apatinib and ATF4 silencing abolished glutamine metabolism in NSCLC cells. | |||
Thyroid cancer [ICD-11: 2D10]
| Drug Resistance Data Categorized by Their Corresponding Mechanisms | ||||
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Unusual Activation of Pro-survival Pathway (UAPP)
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| Key Molecule: Forkhead box K2 (FOXK2) | [1] | |||
| Resistant Disease | Anaplastic thyroid cancer [ICD-11: 2D10.2] | |||
| Molecule Alteration | Expression | Up-regulation |
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| Experimental Note | Identified from the Human Clinical Data | |||
| Cell Pathway Regulation | VEGFA/VEGFR1 signaling pathway | Activation | hsa05205 | |
| In Vitro Model | SkOV3 cells | Ovary | Homo sapiens (Human) | CVCL_0532 |
| H1975 cells | Lung | Homo sapiens (Human) | CVCL_1511 | |
| A2780 cells | Ovary | Homo sapiens (Human) | CVCL_0134 | |
| U2OS cells | Bone | Homo sapiens (Human) | CVCL_0042 | |
| HUT78 cells | Lymph | Homo sapiens (Human) | CVCL_0337 | |
| SH-1-V2 cells | Esophagus | Homo sapiens (Human) | N.A. | |
| In Vivo Model | Nude mouse xenograft model | Mus musculus | ||
| Experiment for Molecule Alteration |
Western blot analysis | |||
| Experiment for Drug Resistance |
CCK-8 assay | |||
| Mechanism Description | On VEGFR2 blockage by specific targeting agent, such as Apatinib, FOXK2 could rapidly trigger therapeutic resistance. Mechanical analyses revealed that VEGFA transcriptionally induced by FOXK2 could bind to VEGFR1 as a compensation for VEGFR2 blockage, which promoted angiogenesis by activating ERK, PI3K/AKT and P38/MAPK signaling in human umbilical vein endothelial cells (HUVECs). Synergic effect on anti-angiogenesis could be observed when VEGFR1 suppressor AF321 was included in VEGFR2 inhibition system, which clarified the pivot role of FOXK2 in VEGFR2 targeting therapy resistance. | |||
| Key Molecule: Vascular endothelial growth factor A (VEGFA) | [1] | |||
| Resistant Disease | Anaplastic thyroid cancer [ICD-11: 2D10.2] | |||
| Molecule Alteration | Expression | Up-regulation |
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| Experimental Note | Identified from the Human Clinical Data | |||
| Cell Pathway Regulation | VEGFA/VEGFR1 signaling pathway | Activation | hsa05205 | |
| In Vitro Model | SkOV3 cells | Ovary | Homo sapiens (Human) | CVCL_0532 |
| H1975 cells | Lung | Homo sapiens (Human) | CVCL_1511 | |
| A2780 cells | Ovary | Homo sapiens (Human) | CVCL_0134 | |
| U2OS cells | Bone | Homo sapiens (Human) | CVCL_0042 | |
| HUT78 cells | Lymph | Homo sapiens (Human) | CVCL_0337 | |
| SH-1-V2 cells | Esophagus | Homo sapiens (Human) | N.A. | |
| In Vivo Model | Nude mouse xenograft model | Mus musculus | ||
| Experiment for Molecule Alteration |
Western blot analysis | |||
| Experiment for Drug Resistance |
CCK-8 assay | |||
| Mechanism Description | On VEGFR2 blockage by specific targeting agent, such as Apatinib, FOXK2 could rapidly trigger therapeutic resistance. Mechanical analyses revealed that VEGFA transcriptionally induced by FOXK2 could bind to VEGFR1 as a compensation for VEGFR2 blockage, which promoted angiogenesis by activating ERK, PI3K/AKT and P38/MAPK signaling in human umbilical vein endothelial cells (HUVECs). Synergic effect on anti-angiogenesis could be observed when VEGFR1 suppressor AF321 was included in VEGFR2 inhibition system, which clarified the pivot role of FOXK2 in VEGFR2 targeting therapy resistance. | |||
References
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