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Type
HazMat fee for 500 gram (Estimated)
Excepted Quantity
USD 0.00
Limited Quantity
USD 15-60
Inaccessible (Haz class 6.1), Domestic
USD 80+
Inaccessible (Haz class 6.1), International
USD 150+
Accessible (Haz class 3, 4, 5 or 8), Domestic
USD 100+
Accessible (Haz class 3, 4, 5 or 8), International
ALK (anaplastic lymphoma kinase) is a tyrosine kinase that is constitutively activated in certain cancers, following gene alterations such as chromosomal translocation, amplification or point mutation. Ceritinib is a selective inhibitor of ALK with IC50 value of 0.2nM (measured by enzymatic kinase activity), and less potent to FLT3, IGF-1R, InsR and STK22D with IC50 values of 60nM, 8nM, 7nM and 23nM, respectively, and showed inhibitory activity on celluar kinase in Ba/F3 cells with IC50 values of 40.7nM, 2.2nM, 410nM and 141.8nM for Tel-ALK, EML4-ALK, Tel-IGF-1R and Tel-Ros, respectively. The cell proliferation study showed that Ceritinib exhibited preferential anti-proliferative activity in Ba/F3 cells expressing NPM-ALK (26nM) and in Karpas299 cells with NPM-ALK fusion (22.8nM)[1]. As the second generation of ALK inhibitor, Ceritinib can overcome several crizotinib resistant mutations in non–small cell lung cancers, including in two ALK-rearranged lung cancer cell lines H3122 and H2228, ALK-mutant cells, H3122 CR1 (L1196M), MGH021-4 (G1269A) and MGH045 (L1196M) cells, as well as ALK wild-type (WT) crizotinib-resistant MGH051 cells from patient, and lead inhibition on p-ALK, p-AKT, p-ERK,p-S6 and cell proliferation at much lower dose than Crizotinib. Consistent with the in vitro study, ceritinib showed more potent anti-tumor activity at dose (50mg/kg) lower than crizotinib (100mg/kg) in mice bearing crizotinib-resistant tumors harboring EML4–ALK wild-type, I1171T, or C1156Y mutations[2].
To evaluate the effect of Ceritinib on the growth of A375X1 cells, results showed that Ceritinib combined with BRAF inhibitor significantly suppressed cell proliferation.
Mol Cancer. 2018 Oct 5;17(1):145.
BRAF/NRAS-WT melanoma cell lines
0.5 or 2.5μM
72 h
Ceritinib enhanced the efficacy of trametinib across the majority of the BRAF/NRAS-WT cell lines, and the combination showed increased cytotoxicity in both 3D spheroid culture and long-term colony formation experiments.
Mol Cancer Ther. 2018 Jan;17(1):73-83.
OVCAR-8
0.75 μM
8-10 days
Ceritinib synergized with the PARPi olaparib in HR-proficient OVCAR-8 cells, inducing tumor cell death
Cancer Res. 2022 Jan 15;82(2):307-319.
COV362
0.75 μM
8-10 days
Ceritinib synergized with the PARPi olaparib in BRCA1-mutant COV362 cells, inducing tumor cell death
Cancer Res. 2022 Jan 15;82(2):307-319.
PC3
0.75 μM
8-10 days
Ceritinib synergized with the PARPi olaparib in prostate cancer PC3 cells, inducing tumor cell death
Cancer Res. 2022 Jan 15;82(2):307-319.
MDA-MB-231
0.75 μM
8-10 days
Ceritinib did not synergize with the PARPi olaparib in breast cancer MDA-MB-231 cells
Cancer Res. 2022 Jan 15;82(2):307-319.
OVCAR-8
0.75 μM
8-10 days
Ceritinib synergized with the PARPi olaparib in HR-proficient OVCAR-8 cells, inhibiting cell proliferation.
Cancer Res. 2022 Jan 15;82(2):307-319.
COV362
0.75 μM
8-10 days
Ceritinib synergized with the PARPi olaparib in BRCA1-mutant COV362 cells, inhibiting cell proliferation.
Cancer Res. 2022 Jan 15;82(2):307-319.
Ba/F3 cells
300, 600, 1000 nM
2-4 weeks
Identify ceritinib- or lorlatinib-resistant ALK-compound mutations through ENU mutagenesis screening and evaluate their sensitivity to ALK-TKIs.
EBioMedicine. 2019 Mar;41:105-119.
Ba/F3 cells
300, 600, or 1000 nM
3 h
Assess the effect of ALK-TKIs on ALK phosphorylation and downstream signaling in Ba/F3 cells, confirming resistance of ALK-G1202R + G1269A double mutation to lorlatinib.
EBioMedicine. 2019 Mar;41:105-119.
NCI-H3122 cells
200 nM
2-4 months
To study the evolution of resistance to Ceritinib in NCI-H3122 cells, results showed that cells were able to grow at 200 nM Ceritinib concentration, and resistance gradually increased.
Nat Commun. 2020 May 14;11(1):2393.
H3122 cells
1 µM
6 months
Establishing a Ceritinib-resistant cell model to analyze DNA methylation and transcriptome changes
Exp Mol Med. 2022 Aug;54(8):1236-1249.
NB-1
1.5 nM -10 μM
6 days
To evaluate the anti-proliferative and cytotoxic effects of Ceritinib on NB-1 cells, the results showed that Ceritinib significantly inhibited the proliferation of NB-1 cells.
Elife. 2017 Apr 20;6:e17137.
SH-SY5Y
1.5 nM -10 μM
6 days
To evaluate the anti-proliferative effects of Ceritinib on SH-SY5Y cells, the results showed that Ceritinib reduced the anti-proliferative activity in SH-SY5Y cells.
Elife. 2017 Apr 20;6:e17137.
NB-1643
1.5 nM -10 μM
6 days
To evaluate the anti-proliferative effects of Ceritinib on NB-1643 cells, the results showed that Ceritinib reduced the anti-proliferative activity in NB-1643 cells.
Elife. 2017 Apr 20;6:e17137.
IMR-32
1.5 nM -10 μM
6 days
To evaluate the anti-proliferative effects of Ceritinib on IMR-32 cells, the results showed that Ceritinib reduced the anti-proliferative activity in IMR-32 cells.
Elife. 2017 Apr 20;6:e17137.
Ceritinib/色瑞替尼 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
NOD/SCID gamma mice
A375X1-induced melanoma model
Oral
50 mg/kg
Once daily for 7 consecutive days
To evaluate the effect of Ceritinib combined with BRAF inhibitor on tumor growth, results showed that the combination treatment significantly inhibited tumor growth.
Mol Cancer. 2018 Oct 5;17(1):145.
NSG mice
BRAF/NRAS-WT melanoma xenograft model
Oral
25mg/kg
Daily dosing for 24 days
The combination of ceritinib and trametinib significantly inhibited tumor growth, showing more pronounced effects compared to trametinib or ceritinib monotherapy.
Mol Cancer Ther. 2018 Jan;17(1):73-83.
SCID beige mice
HGSOC patient-derived xenograft (PDX) models
Oral gavage
100 mg/kg
Daily for up to 9 weeks
The combination of ceritinib and olaparib induced tumor regression more effectively than olaparib alone in HGSOC PDX models, particularly in models with preexisting PARPi sensitivity.
Cancer Res. 2022 Jan 15;82(2):307-319.
BALB-c nu/nu mice
JFCR-041-2 cell xenograft model
Oral
10, 30, 50 mg/kg
Once daily for 5-6 days/week
Evaluate the antitumor effect of lorlatinib in the JFCR-041-2 cell xenograft model, finding tumor recurrence after lorlatinib treatment and identifying the ALK-G1202R + G1269A double mutation.
EBioMedicine. 2019 Mar;41:105-119.
CB17 SCID mice
SH-SY5Y and NB-1691 xenograft models
Oral
50 mg/kg
Once daily for 49 days
To evaluate the anti-tumor efficacy of combination therapy with Ceritinib and Ribociclib in neuroblastoma xenograft models, results showed that combination therapy significantly prolonged event-free survival and achieved complete and sustained tumor regressions.
Clin Cancer Res. 2017 Jun 1;23(11):2856-2868
BALB/c nude mice
LR cell xenograft model
Intraperitoneal injection
100 mg/kg
Every 24 hours for 13 days
Evaluate the inhibitory effect of 5fdC on Ceritinib-resistant tumors
Exp Mol Med. 2022 Aug;54(8):1236-1249.
Mice
Neuroblastoma xenograft models
Oral
50 mg/kg
Daily for 60 days
To evaluate the antitumor activity of Ceritinib monotherapy and its combination with CGM097 in neuroblastoma xenograft models, the results showed that the combination significantly inhibited tumor growth and achieved durable tumor regression.
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