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Cabozantinib (XL184) Met/VEGFR2 inhibitor

Name: Cabozantinib (XL184)
Brand: Selleck Chemicals
SKU: S1119
Availability: InStock
Rating: 5 (166 reviews)

Cat.No.S1119

A potent VEGFR2 inhibitor with IC50 of 0.035 nM, Cabozantinib (XL184) also inhibits c-Met, Ret, Kit, Flt-1/3/4, Tie2, and AXL with IC50 of 1.3 nM, 4 nM, 4.6 nM, 12 nM/11.3 nM/6 nM, 14.3 nM and 7 nM in cell-free assays, respectively. It induces PUMA-dependent apoptosis in colon cancer cells via AKT/GSK-3β/NF-κB signaling pathway.

Chemical Structure

Molecular Weight: 501.51

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Quality Control

Batch: Purity: 99.99%

99.99

Related Targets	EGFR PDGFR FGFR c-Met Src MEK CSF-1R FLT3 HER2 c-Kit
Other VEGFR Products	SAR131675 SU5402 Cediranib (AZD2171) Vatalanib (PTK787) 2HCl Linifanib (ABT-869) Anlotinib (AL3818) dihydrochloride Apatinib Apatinib (YN968D1) mesylate Ki8751 ZM 323881 HCl

Cell Culture, Treatment & Working Concentration

Cell Lines	Assay Type	Concentration	Incubation Time	Formulation	Activity Description	PMID
E98NT	Growth Inhibition Assay	0.01-10 μM		DMSO	IC50=89 nM	23484006
SNU-5	Growth Inhibition Assay				IC50= 19 nM	21926191
Hs746T	Growth Inhibition Assay				IC50=9.9 nM	21926191
SNU-1	Growth Inhibition Assay				IC50=5223 nM	21926191
SNU-16	Growth Inhibition Assay				IC50=1149 nM	21926191
MDA-MB-231	Growth Inhibition Assay				IC50= 6421 nM	21926191
U87MG	Growth Inhibition Assay				IC50=1851 nM	21926191
H441	Growth Inhibition Assay				IC50=21700 nM	21926191
H69	Growth Inhibition Assay				IC50=20200 nM	21926191
PC3	Growth Inhibition Assay				IC50=10800 nM	21926191
MTC-TT	Growth Inhibition Assay				IC50=0.04 + 0.03 μM	21470995
MZ-CRC	Growth Inhibition Assay				IC50> 5 μM	21470995
TPC-1	Growth Inhibition Assay				IC50=0.06 + 0.02 μM	21470995
NIH-3T3/TPR-Met	Function assay				Inhibition of cell proliferation in mouse NIH-3T3/TPR-Met cells, IC50 = 1 μM.	24996144
BA/F3	Growth inhibition assay				Inhibition of TEL-fused VEGFR2 (unknown origin) expressed in mouse BA/F3 cells assessed as cell growth inhibition, GI50 = 0.003 μM.	26652860
BaF3	Growth inhibition assay		48 hrs		Inhibition of TEL-fused Ret S891A mutant (unknown origin) expressed in mouse BaF3 cells assessed as cell growth inhibition after 48 hrs by MTT assay, GI50 = 0.01 μM.	26652860
BA/F3	Growth inhibition assay		48 hrs		Inhibition of wild type TEL-fused RET (unknown origin) expressed in mouse BA/F3 cells assessed as cell growth inhibition after 48 hrs by MTT assay, GI50 = 0.05 μM.	26652860
TT	Growth inhibition assay		10 days		Inhibition of RET C634W mutant in human TT cells assessed as cell growth inhibition after 10 days by MTT assay, GI50 = 0.12 μM.	26652860
BA/F3	Growth inhibition assay		48 hrs		Inhibition of TEL-fused Ret V804M mutant (unknown origin) expressed in mouse BA/F3 cells assessed as cell growth inhibition after 48 hrs by MTT assay, GI50 = 0.89 μM.	26652860
BaF3	Growth inhibition assay		48 hrs		Inhibition of TEL-fused Ret V804L mutant (unknown origin) expressed in mouse BaF3 cells assessed as cell growth inhibition after 48 hrs by MTT assay, GI50 = 0.91 μM.	26652860
Nthy-ori 3-1	Cytotoxicity assay		10 days		Cytotoxicity against human Nthy-ori 3-1 cells after 10 days by MTT assay, GI50 = 4.93 μM.	26652860
BAF3	Function assay	0.01 to 10 uM	1 hr		Inhibition of TEL-fused wild type Ret (unknown origin) phosphorylation at Y1062/Y905 expressed in mouse BAF3 cells at 0.01 to 10 uM after 1 hr by Western blot analysis	26652860
TT	Function assay		4 hrs		Inhibition of autophosphorylation of RET C634W mutant at Y905 in human TT cells at 1 uM after 4 hrs by Western blot analysis	26652860
BAF3	Function assay	0.01 to 10 uM	1 hr		Inhibition of TEL-fused Ret S891A mutant (unknown origin) phosphorylation at Y1062/Y905 expressed in mouse BAF3 cells at 0.01 to 10 uM after 1 hr by Western blot analysis	26652860
BAF3	Function assay	0.01 to 10 uM	1 hr		Inhibition of TEL-fused Ret S891A mutant (unknown origin) expressed in mouse BAF3 cells assessed as suppression of phosphorylation of PLCgamma at Y783 at 0.01 to 10 uM after 1 hr by Western blot analysis	26652860
BAF3	Function assay	0.01 to 10 uM	1 hr		Inhibition of TEL-fused Ret S891A mutant (unknown origin) expressed in mouse BAF3 cells assessed as suppression of phosphorylation of Shc at Y317 at 0.01 to 10 uM after 1 hr by Western blot analysis	26652860
TT	Function assay	1 to 10 uM	4 hrs		Inhibition of RET C634W mutant in human TT cells assessed as suppression of PLCgamma phosphorylation at Y783 at 1 to 10 uM after 4 hrs by Western blot analysis	26652860
TT	Function assay	1 to 10 uM	4 hrs		Inhibition of RET C634W mutant in human TT cells assessed as suppression of ERK phosphorylation at T202/Y204 at 1 to 10 uM after 4 hrs by Western blot analysis	26652860
TT	Function assay	1 to 10 uM	4 hrs		Inhibition of RET C634W mutant in human TT cells assessed as suppression of AKT phosphorylation at T308/S473 at 1 to 10 uM after 4 hrs by Western blot analysis	26652860
TT	Function assay	1 uM			Inhibition of Ret-driven oncogenic transformation of human TT cells at 1 uM by soft agar assay	26652860
TT	Function assay	1 uM	4 hrs		Inhibition of autophosphorylation of RET C634W mutant at Y1062 in human TT cells at 1 uM after 4 hrs by Western blot analysis	26652860
TT	Apoptosis assay	1 uM	96 hrs		Induction of apoptosis in human TT cells expressing Ret C634W mutant at 1 uM after 96 hrs by annexinV/PI staining-based flow cytometric analysis	26652860
PC3	Function assay		1 to 3 hrs		Inhibition of c-Met phosphorylation in human PC3 cells incubated for 1 to 3 hrs, IC50 = 1.9 μM.	26717201
MDA-MB-231	Function assay		1 to 3 hrs		Inhibition of AXL phosphorylation in human MDA-MB-231 cells incubated for 1 to 3 hrs, IC50 = 5 μM.	26717201
BAF3	Function assay		1 to 3 hrs		Inhibition of FLT3 (unknown origin) phosphorylation transfected in mouse BAF3 cells incubated for 1 to 3 hrs, IC50 = 7.5 μM.	26717201
MDA-MB-231	Function assay		1 to 3 hrs		Inhibition of KIT (unknown origin) phosphorylation transfected in human MDA-MB-231 cells incubated for 1 to 3 hrs, IC50 = 42 μM.	26717201
BA/F3	Function assay		48 hrs		Inhibition of KDR (unknown origin) expressed in mouse BA/F3 cells assessed as reduction in cell viability after 48 hrs by Cell titre glo-based luminescence assay, IC50 = 0.014 μM.	26874741
Sf21	Function assay		15 mins		Inhibition of recombinant His-tagged human KDR expressed in insect Sf21 cells preincubated for 15 mins followed by substrate addition measured after 20 mins by HTRF assay, IC50 = 0.016 μM.	26874741
BA/F3	Function assay		48 hrs		Inhibition of KIF5B/RET (unknown origin) expressed in mouse BA/F3 cells assessed as reduction in cell viability after 48 hrs by Cell titre glo-based luminescence assay, IC50 = 0.19 μM.	26874741
BA/F3	Function assay		48 hrs		Inhibition of KIF5B/RET (unknown origin) expressed in mouse BA/F3 cells assessed as reduction in cell viability after 48 hrs by Cell titre glo-based luminescence assay, IC50 = 0.19 μM.	26874741
BA/F3	Antiproliferative assay		72 hrs		Antiproliferative activity against mouse BA/F3 cells expressing TPR-Met after 72 hrs by CCK8 assay, IC50 = 0.0219 μM.	27068889
Sf21	Function assay		60 mins		Inhibition of wild type N-terminal GST-tagged recombinant human RET (658 residues) expressed in insect Sf21 cells using poly(Glu,Tyr)4:1 as substrate incubated for 60 mins by ELISA, IC50 = 0.003 μM.	27131066
Sf21	Function assay		60 mins		Inhibition of N-terminal GST-tagged recombinant human RET V804M mutant (658 residues) expressed in insect Sf21 cells using poly(Glu,Tyr)4:1 as substrate incubated for 60 mins by ELISA, IC50 = 0.811 μM.	27131066
BaF3	Function assay		72 hrs		Inhibition of CCDC6-RET (unknown origin) expressed in mouse BaF3 cells assessed as inhibition of cell proliferation after 72 hrs by SRB/CCK-8 assay, IC50 = 0.889 μM.	27131066
BaF3	Function assay		72 hrs		Inhibition of CCDC6-RET (unknown origin) expressed in mouse BaF3 cells assessed as inhibition of cell proliferation after 72 hrs by SRB/CCK-8 assay, IC50 = 0.889 μM.	27131066
Ba/F3	Function assay				Inhibition of RET (unknown origin) transfected in mouse Ba/F3 cells assessed as reduction in cell viability by CellTiter-Glo luminescence assay, GI50 = 0.07 μM.	27814560
TT	Function assay				Inhibition of RET C634W mutant in human TT cells assessed as reduction in cell viability by CellTiter-Glo luminescence assay, GI50 = 0.26 μM.	27814560
Ba/F3	Function assay				Inhibition of RET V804M mutant (unknown origin) transfected in mouse Ba/F3 cells assessed as reduction in cell viability by CellTiter-Glo luminescence assay, GI50 = 0.74 μM.	27814560
Nthy-ori 3-1	Cytotoxicity assay				Cytotoxicity against human Nthy-ori 3-1 cells assessed as reduction in cell viability by CellTiter-Glo luminescence assay, GI50 = 2.92 μM.	27814560
HepG2	Antiproliferative assay		72 hrs		Antiproliferative activity against human HepG2 cells after 72 hrs by MTT assay, IC50 = 0.012 μM.	28412159
EBC1	Antiproliferative assay		72 hrs		Antiproliferative activity against human EBC1 cells after 72 hrs by MTT assay, IC50 = 0.0514 μM.	28412159
H1299	Growth inhibition assay		72 hrs		Growth inhibition of human H1299 cells incubated for 72 hrs by CCK8 assay, IC50 = 1.919 μM.	28651979
MCF7	Growth inhibition assay		72 hrs		Growth inhibition of human MCF7 cells incubated for 72 hrs by CCK8 assay, IC50 = 2.889 μM.	28651979
A549	Growth inhibition assay		72 hrs		Growth inhibition of human A549 cells incubated for 72 hrs by CCK8 assay, IC50 = 4.205 μM.	28651979
T47D	Growth inhibition assay		72 hrs		Growth inhibition of human T47D cells incubated for 72 hrs by CCK8 assay, IC50 = 4.448 μM.	28651979
H460	Growth inhibition assay		72 hrs		Growth inhibition of human H460 cells incubated for 72 hrs by CCK8 assay, IC50 = 5.669 μM.	28651979
HuH7	Antiproliferative assay		48 hrs		Antiproliferative activity against human HuH7 cells after 48 hrs by MTT assay, IC50 = 4.348 μM.	29057042
A498	Antiproliferative assay		48 hrs		Antiproliferative activity against human A498 cells after 48 hrs by MTT assay, IC50 = 8.456 μM.	29057042
NCI-H727	Antiproliferative assay		48 hrs		Antiproliferative activity against human NCI-H727 cells after 48 hrs by MTT assay, IC50 = 14.01 μM.	29057042
BAF3	Antiproliferative assay		72 hrs		Antiproliferative activity against mouse BAF3 cells harboring TRP-MET after 72 hrs by CCK-8 assay, IC50 = 0.024 μM.	29146452
A549	Cytotoxicity assay	10 uM	72 hrs		Cytotoxicity against human A549 cells at 10 uM after 72 hrs by Incucyte live-cell imaging analysis	29407963
A673	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells	29435139
DAOY	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY cells	29435139
Saos-2	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 cells	29435139
BT-37	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-37 cells	29435139
RD	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD cells	29435139
SK-N-SH	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-SH cells	29435139
BT-12	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-12 cells	29435139
NB1643	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 cells	29435139
OHS-50	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells	29435139
Rh41	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh41 cells	29435139
A673	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for A673 cells)	29435139
U-2 OS	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for U-2 OS cells	29435139
OHS-50	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for OHS-50 cells	29435139
Rh41	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh41 cells	29435139
SJ-GBM2	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 cells	29435139
SK-N-MC	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells	29435139
NB-EBc1	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells	29435139
LAN-5	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells	29435139
Rh18	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh18 cells	29435139
SJ-GBM2	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SJ-GBM2 cells	29435139
TC32	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for TC32 cells	29435139
Saos-2	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Saos-2 cells	29435139
EBC1	Antiproliferative assay		72 hrs		Antiproliferative activity against human EBC1 cells after 72 hrs by MTT assay, IC50 = 0.0048 μM.	30248654
MKN45	Antiproliferative assay		72 hrs		Antiproliferative activity against human MKN45 cells after 72 hrs by MTT assay, IC50 = 0.0069 μM.	30248654
SNU5	Antiproliferative assay		72 hrs		Antiproliferative activity against human SNU5 cells after 72 hrs by MTT assay, IC50 = 0.0121 μM.	30248654
BAF3	Function assay		72 hrs		Inhibition of TPR-tagged met (unknown origin) expressed in mouse BAF3 cells assessed as inhibition of cell proliferation after 72 hrs by MTT assay, IC50 = 0.01986 μM.	30248654
NCI-H460	Antiproliferative assay		72 hrs		Antiproliferative activity against human NCI-H460 cells after 72 hrs by MTT assay, IC50 = 0.0401 μM.	30248654
MGHU3	Antiproliferative assay		72 hrs		Antiproliferative activity against human MGHU3 cells after 72 hrs by CellTiter-Glo assay	30309671
RT112	Antiproliferative assay		72 hrs		Antiproliferative activity against human RT112 cells after 72 hrs by CellTiter-Glo assay	30309671
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Solubility

In vitro
Batch:

DMSO : 100 mg/mL (199.39 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Water : Insoluble

Ethanol : Insoluble

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
Mass value Mass unit	Concentration value Concentration unit	Volume value Volume unit	Molecular weight (g/mol)

Dilution Calculator Molecular Weight Calculator

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Chemical Information, Storage & Stability

Molecular Weight	501.51	Formula	C₂₈H₂₄FN₃O₅	Storage (From the date of receipt)	3 years-20°Cpowder
CAS No.	849217-68-1	Download SDF		Storage of Stock Solutions	1 year-80°Cin solvent 1 month-20°Cin solvent
Synonyms	BMS-907351			Smiles	COC1=CC2=C(C=CN=C2C=C1OC)OC3=CC=C(C=C3)NC(=O)C4(CC4)C(=O)NC5=CC=C(C=C5)F

Mechanism of Action

Targets/IC₅₀/Ki	VEGFR2/KDR (Cell-free assay) 0.035 nM c-Met (Cell-free assay) 1.3 nM Axl (Cell-free assay) 7 nM
In vitro	Cabozantinib (XL184) has weak inhibitory activity against RON and PDGFRβ with IC50 of 124 nM and 234 nM, respectively, and has low activity against FGFR1 with IC50 of 5.294 μM. At low concentration (0.1-0.5 μM), it is sufficient to induce marked inhibition of constitutive and inducible Met phosphorylation and its resultant downstream signaling in MPNST cells, and inhibit HGF-induced MPNST cell migration and invasion. This compound also induces marked inhibition of Met and VEGFR2 phosphorylation in cytokine-stimulated human umbilical vein endothelial cells (HUVECs). Although it has no significant effect on MPNST cell growth at 0.1 μM, XL184 at 5-10 μM significantly inhibits the MPNST cell growth.
In vivo	Cabozantinib (XL184) treatment at 30 mg/kg in RIP-Tag2 mice with spontaneous pancreatic islet tumors disrupts 83% of the tumor vasculature, reduces pericytes and empty basement membrane sleeves, causes widespread intratumoral hypoxia and extensive tumor cell apoptosis, and slows regrowth of the tumor vasculature after drug withdrawal, more significantly compared with XL999 that blocks VEGFR but not c-Met, leading to only 43% reduction in vascularity, suggesting that concurrent inhibition of VEGFR and other functionally relevant receptor tyrosine kinases (RTK) amplifies angiogenesis inhibition. This compound also decreases invasiveness of primary tumors and reduces metastasis. At 30 mg/kg/day, it significantly abrogates human MPNST xenografts growth and metastasis in SCID mice. Administration of XL184 induces dose-dependent inhibition of tumor growth in breast, lung, and glioma tumor models, in association with decreased tumor and endothelial cell proliferation as well as increased apoptosis. A single oral dose is sufficient to induce sustained tumor growth inhibition in MDA-MB-231 tumor-bearing mice and C6 tumor-bearing rats at 100 mg/kg and 10 mg/kg, respectively.
References	[1] https://pubmed.ncbi.nlm.nih.gov/21613405/ [2] https://pubmed.ncbi.nlm.nih.gov/21540237/ [3] https://pubmed.ncbi.nlm.nih.gov/21926191/

Applications

Methods	Biomarkers	PMID
Western blot	p-MET(Y1234/1235) / MET / p-EGFR(Y1068) / EGFR / p-Gab1(Y627) / Gab1 / p-AKT(S473) / p-ERK / p-EIF4E p-MET / p-ERK / p-AKT	29188469
Immunofluorescence	α-tubulin	29520051
Growth inhibition assay	Cell viability	23661005

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2024-05-22)

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT06156410	Recruiting	Ewing Sarcoma\|Osteosarcoma	Children''s Hospital of Philadelphia\|Children''s Hospital Colorado\|Exelixis\|Alex''s Lemonade Stand Foundation	October 24 2023	Phase 1
NCT05249114	Active not recruiting	Neuroendocrine Tumors	Providence Health & Services\|Exelixis\|Advanced Accelerator Applications SA	December 28 2022	Phase 1
NCT05444933	Completed	Advanced Renal Cell Carcinoma	Ipsen	September 16 2022	--

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