InterPAD - DETAILS

MAVPFVEDWDLVQTLGEGAYGEVQLAVNRVTEEAVAVKIVDMKRAVDCPENIKKEICINK
MLNHENVVKFYGHRREGNIQYLFLEYCSGGELFDRIEPDIGMPEPDAQRFFHQLMAGVVY
LHGIGITHRDIKPENLLLDERDNLKISDFGLATVFRYNNRERLLNKMCGTLPYVAPELLK
RREFHAEPVDVWSCGIVLTAMLAGELPWDQPSDSCQEYSDWKEKKTYLNPWKKIDSAPLA
LLHKILVENPSARITIPDIKKDRWYNKPLKKGAKRPRVTSGGVSESPSGFSKHIQSNLDF
SPVNSASSEENVKYSSSQPEPRTGLSLWDTSPSYIDKLVQGISFSQPTCPDHMLLNSQLL
GTPGSSQNPWQRLVKRMTRFFTKLDADKSYQCLKETCEKLGYQWKKSCMNQVTISTTDRR
NNKLIFKVNLLEMDDKILVDFRLSKGDGLEFKRHFLKIKGKLIDIVSSQKIWLPAT

No.	Title	Href
1	Betulinic acid, a major therapeutic triterpene of Celastrus orbiculatus Thunb., acts as a chemosensitizer of gemcitabine by promoting Chk1 degradation. J Ethnopharmacol. 2023 Jun 12;309:116295. doi: 10.1016/j.jep.2023.116295.	`Click`
2	Our data indicate that BMDC has the potential to improve the treatment of primary EGFR-TKI resistant NISCLC that cannot be controlled with single-target agent, such as icotinib.	`Click`
3	Synthetic lethality of combined AT-101 with idarubicin in acute myeloid leukemia via blockade of DNA repair and activation of intrinsic apoptotic pathway. Cancer Lett. 2019 Oct 1;461:31-43. doi: 10.1016/j.canlet.2019.07.003.	`Click`
4	Patchouli alcohol induces G0 /G1 cell cycle arrest and apoptosis in vincristine-resistant non-small cell lung cancer through ROS-mediated DNA damage. Thorac Cancer. 2023 Jul;14(21):2007-2017. doi: 10.1111/1759-7714.14982.	`Click`
5	Pristimerin synergizes with gemcitabine through abrogating Chk1/53BP1-mediated DNA repair in pancreatic cancer cells. Food Chem Toxicol. 2021 Jan;147:111919. doi: 10.1016/j.fct.2020.111919.	`Click`
6	Inhibitory effects of Silibinin combined with doxorubicin in hepatocellular carcinoma; an in vivo study. J BUON. 2016 Jul-Aug;21(4):917-924.	`Click`
7	Zeylenone synergizes with cisplatin in osteosarcoma by enhancing DNA damage, apoptosis, and necrosis via the Hsp90/AKT/GSK3β and Fanconi anaemia pathway. Phytother Res. 2021 Oct;35(10):5899-5918. doi: 10.1002/ptr.7299	`Click`
8	Artesunate improves venetoclax plus cytarabine AML cell targeting by regulating the Noxa/Bim/Mcl-1/p-Chk1 axis. Cell Death Dis. 2022 Apr 20;13(4):379. doi: 10.1038/s41419-022-04810-z.	`Click`
9	Mitocurcumin utilizes oxidative stress to upregulate JNK/p38 signaling and overcomes Cytarabine resistance in acute myeloid leukemia. Cell Signal. 2024;114:111004. doi:10.1016/j.cellsig.2023.111004	`Click`

No.

Title

Href

Betulinic acid, a major therapeutic triterpene of Celastrus orbiculatus Thunb., acts as a chemosensitizer of gemcitabine by promoting Chk1 degradation. J Ethnopharmacol. 2023 Jun 12;309:116295. doi: 10.1016/j.jep.2023.116295.

Click

Our data indicate that BMDC has the potential to improve the treatment of primary EGFR-TKI resistant NISCLC that cannot be controlled with single-target agent, such as icotinib.

Click

Synthetic lethality of combined AT-101 with idarubicin in acute myeloid leukemia via blockade of DNA repair and activation of intrinsic apoptotic pathway. Cancer Lett. 2019 Oct 1;461:31-43. doi: 10.1016/j.canlet.2019.07.003.

Click

Patchouli alcohol induces G0 /G1 cell cycle arrest and apoptosis in vincristine-resistant non-small cell lung cancer through ROS-mediated DNA damage. Thorac Cancer. 2023 Jul;14(21):2007-2017. doi: 10.1111/1759-7714.14982.

Click

Pristimerin synergizes with gemcitabine through abrogating Chk1/53BP1-mediated DNA repair in pancreatic cancer cells. Food Chem Toxicol. 2021 Jan;147:111919. doi: 10.1016/j.fct.2020.111919.

Click

Inhibitory effects of Silibinin combined with doxorubicin in hepatocellular carcinoma; an in vivo study. J BUON. 2016 Jul-Aug;21(4):917-924.

Click

Zeylenone synergizes with cisplatin in osteosarcoma by enhancing DNA damage, apoptosis, and necrosis via the Hsp90/AKT/GSK3β and Fanconi anaemia pathway. Phytother Res. 2021 Oct;35(10):5899-5918. doi: 10.1002/ptr.7299

Click

Artesunate improves venetoclax plus cytarabine AML cell targeting by regulating the Noxa/Bim/Mcl-1/p-Chk1 axis. Cell Death Dis. 2022 Apr 20;13(4):379. doi: 10.1038/s41419-022-04810-z.

Click

Mitocurcumin utilizes oxidative stress to upregulate JNK/p38 signaling and overcomes Cytarabine resistance in acute myeloid leukemia. Cell Signal. 2024;114:111004. doi:10.1016/j.cellsig.2023.111004

Click

Name	Serine/threonine-protein kinase Chk1
UniProt ID	CHK1_HUMAN
Gene Name	CHEK1
Gene ID	1111
Synonyms	CHEK1, CHK1, OZEMA21
Sequence	MAVPFVEDWDLVQTLGEGAYGEVQLAVNRVTEEAVAVKIVDMKRAVDCPENIKKEICINK MLNHENVVKFYGHRREGNIQYLFLEYCSGGELFDRIEPDIGMPEPDAQRFFHQLMAGVVY LHGIGITHRDIKPENLLLDERDNLKISDFGLATVFRYNNRERLLNKMCGTLPYVAPELLK RREFHAEPVDVWSCGIVLTAMLAGELPWDQPSDSCQEYSDWKEKKTYLNPWKKIDSAPLA LLHKILVENPSARITIPDIKKDRWYNKPLKKGAKRPRVTSGGVSESPSGFSKHIQSNLDF SPVNSASSEENVKYSSSQPEPRTGLSLWDTSPSYIDKLVQGISFSQPTCPDHMLLNSQLL GTPGSSQNPWQRLVKRMTRFFTKLDADKSYQCLKETCEKLGYQWKKSCMNQVTISTTDRR NNKLIFKVNLLEMDDKILVDFRLSKGDGLEFKRHFLKIKGKLIDIVSSQKIWLPAT
Pathway Map	`MAP LINK`
KEGG ID	hsa1111
TTD ID	T62449
Pfam	PF00069; PF03109; PF07714; PF14531

Pair Name	Betulinic Acid, Gemcitabine
Phytochemical	Betulinic Acid
Drug	Gemcitabine
Disease Info	[ICD-11: 2A00-2F9Z]	Solid tumour or cancer	Investigative
Regulate Info	Down-regulation	Serine/threonine-protein kinase Chk1	Phosphorylation
Result	These data provide evidence that betulinic acid is a potential candidate for chemosensitization as a naturally occurring Chk1 inhibitor and warrants further preclinical evaluation.

Pair Name	Bisdemethoxycucurmin, Icotinib
Phytochemical	Bisdemethoxycucurmin
Drug	Icotinib
Disease Info	[ICD-11: 2C25]	Lung cancer	Investigative
Regulate Info	Up-regulation	Serine/threonine-protein kinase Chk1	Phosphorylation
Result	Our data indicate that BMDC has the potential to improve the treatment of primary EGFR-TKI resistant NISCLC that cannot be controlled with single-target agent, such as icotinib.

Pair Name	Gossypol, Idarubicin
Phytochemical	Gossypol
Drug	Idarubicin
Disease Info	[ICD-11: 2A60.Z]	Acute myeloid leukemia	Investigative
Regulate Info	Down-regulation	Serine/threonine-protein kinase Chk1	Phosphorylation
Result	These findings suggest that combinatorial therapy with AT-101 and IDA selectively eliminates leukemia stem-like cells both in vitro and in vivo, representing a potent and alternative salvage therapy for the treatment of relapsed and refractory patients with AML.

Pair Name	Patchouli alcohol, Vincristine
Phytochemical	Patchouli alcohol
Drug	Vincristine
Disease Info	[ICD-11: 2C25]	Lung cancer	Investigative
Regulate Info	Up-regulation	Serine/threonine-protein kinase Chk1	Phosphorylation
Result	Patchouli alcohol induces G0 /G1 cell cycle arrest and apoptosis in vincristine-resistant non-small cell lung cancer through ROS-mediated DNA damage

Pair Name	Pristimerin, Gemcitabine
Phytochemical	Pristimerin
Drug	Gemcitabine
Disease Info	[ICD-11: 2C10.0]	Pancreatic ductal adenocarcinoma	Investigative
Regulate Info	Down-regulation	Serine/threonine-protein kinase Chk1	Phosphorylation
Result	These results show that pristimerin acts as a naturally occurring inhibitor of RSR, and a novel therapeutic strategy of combining pristimerin and gemcitabine deserves further detailed investigation in PC models in vivo.

Pair Name	Silibinin, Doxorubicin
Phytochemical	Silibinin
Drug	Doxorubicin
Disease Info	[ICD-11: 2C12]	Hepatocellular carcinoma	Investigative
Regulate Info	Up-regulation	Serine/threonine-protein kinase Chk1	Expression
Result	Inhibitory effects of Silibinin combined with doxorubicin in hepatocellular carcinoma; an in vivo study

Pair Name	Zeylenone, Cisplatin
Phytochemical	Zeylenone
Drug	Cisplatin
Disease Info	[ICD-11: 2B51]	Osteosarcoma	Investigative
Regulate Info	Up-regulation	Serine/threonine-protein kinase Chk1	Expression
Result	Zeylenone synergizes with cisplatin in osteosarcoma by enhancing DNA damage, apoptosis, and necrosis via the Hsp90/AKT/GSK3β and Fanconi anaemia pathway

Pair Name	Artesunate, Venetoclax
Phytochemical	Artesunate
Drug	Venetoclax
Disease Info	[ICD-11: 2A60.Z]	Acute myeloid leukemia	Investigative
Regulate Info	Down-regulation	Serine/threonine-protein kinase Chk1	Phosphorylation
Result	We provide a new triple combination for AML treatment by targeting the Noxa/Mcl-1/Bim axis to reverse Mcl-1/p-Chk1 resistance of cytarabine therapy.

Pair Name	Mitocurcumin, Cytarabine
Phytochemical	Mitocurcumin
Drug	Cytarabine
Disease Info	[ICD-11: 2B33.4]	Leukemia	Investigative
Regulate Info	Down-regulation	Serine/threonine-protein kinase Chk1	Expression
Result	The data suggest that MitoC exploits stress-induced leukemic oxidative environment to up-regulate JNK/p38 signaling to lead to apoptosis and can potentially overcome Cytarabine resistance via ROS/p21/CHK1 axis.