NPASS Compound

Structure

NPC473363 OpenBabel07101718332D 68 80 0 0 1 0 0 0 0 0999 V2000 -14.1120 -7.8781 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2601 0.2601 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -17.0663 -8.5962 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6942 0.9781 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -10.2841 -5.3090 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.0880 -2.3090 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -12.4755 -6.7226 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8966 -0.8955 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -11.1502 -2.8090 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2219 -4.8090 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -12.0162 -3.3090 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3559 -4.3090 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.4181 -2.8090 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.9540 -4.8090 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -11.1502 -5.8090 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2219 -1.8090 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -13.8333 -4.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5388 -3.1180 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.4181 -4.8090 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.9540 -2.8090 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -16.9109 -7.1180 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5388 -0.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -16.1152 -8.9052 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7431 1.2872 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -14.4210 -6.9271 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.9511 -0.6910 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -10.2841 -3.3090 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -5.0880 -4.3090 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -12.0162 -4.3090 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.3559 -3.3090 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -11.1502 -4.8090 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.2219 -2.8090 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -12.8822 -4.8090 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4899 -2.8090 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.5521 -3.3090 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.8200 -4.3090 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.5521 -4.3090 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.8200 -3.3090 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -12.0162 -6.3090 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.3559 -1.3090 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -16.3232 -6.3090 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 0.9511 -1.3090 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -14.4210 -5.3090 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.9511 -2.3090 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -16.3232 -7.9271 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 0.9511 0.3090 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -10.2841 -4.3090 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -5.0880 -3.3090 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -12.8822 -5.8090 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.4899 -1.8090 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -13.8333 -6.1180 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.5388 -1.5000 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -15.3721 -6.6180 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.0000 -1.0000 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -7.6861 -4.8090 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -7.6861 -2.8090 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -16.8584 -9.5743 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.4863 1.9563 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -12.0162 -7.3090 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.3559 -0.3090 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -16.6322 -5.3580 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.2601 -2.2601 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -13.2455 -6.9271 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.1266 -0.6910 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -15.3721 -5.6180 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.0000 -2.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -15.3721 -7.6180 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 -0.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1 25 1 0 0 0 0 2 26 1 0 0 0 0 7 49 1 0 0 0 0 8 50 1 0 0 0 0 9 11 1 0 0 0 0 9 27 1 0 0 0 0 10 12 1 0 0 0 0 10 28 1 0 0 0 0 13 27 1 0 0 0 0 13 35 1 0 0 0 0 14 28 1 0 0 0 0 14 36 1 0 0 0 0 15 31 1 0 0 0 0 15 39 1 0 0 0 0 16 32 1 0 0 0 0 16 40 1 0 0 0 0 17 33 2 0 0 0 0 17 43 1 0 0 0 0 18 34 2 0 0 0 0 18 44 1 0 0 0 0 19 37 1 0 0 0 0 19 47 1 0 0 0 0 20 38 1 0 0 0 0 20 48 1 0 0 0 0 21 41 1 0 0 0 0 21 45 1 0 0 0 0 22 42 1 0 0 0 0 22 46 1 0 0 0 0 23 45 1 0 0 0 0 23 57 1 0 0 0 0 24 46 1 0 0 0 0 24 58 1 0 0 0 0 25 51 1 6 0 0 0 25 53 1 0 0 0 0 26 52 1 6 0 0 0 26 54 1 0 0 0 0 27 47 1 1 0 0 0 28 48 1 1 0 0 0 29 11 1 6 0 0 0 29 31 1 0 0 0 0 29 33 1 0 0 0 0 30 12 1 6 0 0 0 30 32 1 0 0 0 0 30 34 1 0 0 0 0 31 47 1 1 0 0 0 32 48 1 1 0 0 0 33 49 1 0 0 0 0 34 50 1 0 0 0 0 35 37 2 0 0 0 0 35 56 1 0 0 0 0 36 38 1 0 0 0 0 36 55 2 0 0 0 0 37 55 1 0 0 0 0 38 56 2 0 0 0 0 39 49 1 1 0 0 0 39 59 1 0 0 0 0 40 50 1 1 0 0 0 40 60 1 0 0 0 0 41 53 1 1 0 0 0 41 61 1 0 0 0 0 42 54 1 1 0 0 0 42 62 1 0 0 0 0 43 51 1 1 0 0 0 43 65 1 0 0 0 0 44 52 1 1 0 0 0 44 66 1 0 0 0 0 45 3 1 1 0 0 0 45 67 1 0 0 0 0 46 4 1 1 0 0 0 46 68 1 0 0 0 0 47 5 1 1 0 0 0 48 6 1 1 0 0 0 49 51 1 6 0 0 0 50 52 1 6 0 0 0 51 63 1 6 0 0 0 52 64 1 6 0 0 0 53 65 1 1 0 0 0 53 67 1 0 0 0 0 54 66 1 1 0 0 0 54 68 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	944.54
Volume:	945.6
LogP:	3.81
LogD:	2.11
LogS:	-4.709
# Rotatable Bonds:	2
TPSA:	224.54
# H-Bond Aceptor:	14
# H-Bond Donor:	8
# Rings:	13
# Heavy Atoms:	14

MedChem Properties

QED Drug-Likeness Score:	0.199
Synthetic Accessibility Score:	7.912
Fsp3:	0.852
Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Accepted
GSK Rule:	Rejected
BMS Rule:	1
Golden Triangle Rule:	Rejected
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-5.98
MDCK Permeability:	3.9276554161915556e-05
Pgp-inhibitor:	0.178
Pgp-substrate:	1.0
Human Intestinal Absorption (HIA):	0.511
20% Bioavailability (F20%):	0.963
30% Bioavailability (F30%):	0.847

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.165
Plasma Protein Binding (PPB):	62.548667907714844%
Volume Distribution (VD):	0.382
Pgp-substrate:	13.135308265686035%

ADMET: Metabolism

CYP1A2-inhibitor:	0.001
CYP1A2-substrate:	0.925
CYP2C19-inhibitor:	0.002
CYP2C19-substrate:	0.716
CYP2C9-inhibitor:	0.016
CYP2C9-substrate:	0.002
CYP2D6-inhibitor:	0.0
CYP2D6-substrate:	0.081
CYP3A4-inhibitor:	0.961
CYP3A4-substrate:	0.589

ADMET: Excretion

Clearance (CL):	4.788
Half-life (T1/2):	0.222

ADMET: Toxicity

hERG Blockers:	0.618
Human Hepatotoxicity (H-HT):	0.992
Drug-inuced Liver Injury (DILI):	0.037
AMES Toxicity:	0.013
Rat Oral Acute Toxicity:	0.992
Maximum Recommended Daily Dose:	0.996
Skin Sensitization:	0.884
Carcinogencity:	0.831
Eye Corrosion:	0.003
Eye Irritation:	0.005
Respiratory Toxicity:	0.994

Download Data

Data Type	Select
General Info & Identifiers & Properties
Structure MOL file
Source Organisms
Biological Activities
Similar NPs/Drugs

Natural Product: NPC473363

Natural Product ID:	NPC473363
*Common Name:**	Cephalostatin 12
IUPAC Name:	n.a.
Synonyms:	Cephalostatin 12
Standard InCHIKey:	NVRMDLWDRHEFNO-LGANMPMMSA-N
Standard InCHI:	InChI=1S/C54H76N2O12/c1-25-51(63)43(65-53(25)41(61)21-45(3,23-57)67-53)17-33-29-11-9-27-13-35-37(19-47(27,5)31(29)15-39(59)49(33,51)7)55-36-14-28-10-12-30-32(48(28,6)20-38(36)56-35)16-40(60)50(8)34(30)18-44-52(50,64)26(2)54(66-44)42(62)22-46(4,24-58)68-54/h17-18,25-32,39-44,57-64H,9-16,19-24H2,1-8H3/t25-,26-,27-,28-,29+,30+,31-,32-,39+,40+,41+,42+,43-,44-,45-,46-,47-,48-,49+,50+,51+,52+,53-,54-/m0/s1
SMILES:	CC1C2(C(CC(O2)(C)CO)O)OC3C1(C4(C(CC5C(C4=C3)CCC6C5(CC7=C(C6)N=C8CC9(C(CCC1C9CC(C2(C1=CC1C2(C(C2(O1)C(CC(O2)(C)CO)O)C)O)C)O)CC8=N7)C)C)O)C)O
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL403143
PubChem CID:	21774830
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000258] Steroids and steroid derivatives [CHEMONTID:0001295] Hydroxysteroids [CHEMONTID:0003236] 17-hydroxysteroids

*Note: the InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
**Note: the Chemical Classification was calculated by NPClassifier Version 1.5. Reference: PMID:34662515.

Species Source

Organism ID	Organism Name	Taxonomy Level	Family	SuperKingdom	Isolation Part	Collection Location	Collection Time	Reference
NPO25585	Cephalodiscus gilchristi	Species	Cephalodiscidae	Eukaryota	n.a.	n.a.	n.a.	PMID[21899266]
NPO25585	Cephalodiscus gilchristi	Species	Cephalodiscidae	Eukaryota	n.a.	n.a.	n.a.	PMID[22607450]
NPO25585	Cephalodiscus gilchristi	Species	Cephalodiscidae	Eukaryota	n.a.	n.a.	1990	PMID[26042639]
NPO25585	Cephalodiscus gilchristi	Species	Cephalodiscidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]

☑ Note for Reference:
In addition to directly collecting NP source organism data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated them from below databases:
☉ UNPD: Universal Natural Products Database [PMID: 23638153].
☉ StreptomeDB: a database of streptomycetes natural products [PMID: 33051671].
☉ TM-MC: a database of medicinal materials and chemical compounds in Northeast Asian traditional medicine [PMID: 26156871].
☉ TCM@Taiwan: a Traditional Chinese Medicine database [PMID: 21253603].
☉ TCMID: a Traditional Chinese Medicine database [PMID: 29106634].
☉ TCMSP: The traditional Chinese medicine systems pharmacology database and analysis platform [PMID: 24735618].
☉ HerDing: a herb recommendation system to treat diseases using genes and chemicals [PMID: 26980517].
☉ MetaboLights: a metabolomics database [PMID: 27010336].
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

NP Quantity Composition/Concentration

Organism ID	NP ID	Organism Material Preparation	Organism Part	NP Quantity (Standard)	NP Quantity (Minimum)	NP Quantity (Maximum)	Quantity Unit	Reference

☑ Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP quantitative records for specific NP domains (e.g., NPS from foods or herbs) from domain-specific databases. These databases include:
☉ DUKE: Dr. Duke's Phytochemical and Ethnobotanical Databases.
☉ PHENOL EXPLORER: is the first comprehensive database on polyphenol content in foods [PMID: 24103452], its homepage can be accessed at here.
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

Biological Activity

Activity Type	# Activity
ED50	3
GI50	7

Activity Type	# Activity
Cell Line	8
NON-MOLECULAR	2

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT4461	Cell Line	Panel (Carcinoma cell lines)	Homo sapiens	ED50	=	0.072	ug ml-1	PMID[496607]
NPT4461	Cell Line	Panel (Carcinoma cell lines)	Homo sapiens	GI50	=	400.0	nM	PMID[496607]
NPT168	Cell Line	P388	Mus musculus	ED50	=	76.2	nM	PMID[496608]
NPT168	Cell Line	P388	Mus musculus	ED50	=	0.076	uM	PMID[496609]
NPT83	Cell Line	MCF7	Homo sapiens	GI50	=	33.0	nM	PMID[496610]
NPT395	Cell Line	SF-268	Homo sapiens	GI50	=	150.0	nM	PMID[496610]
NPT397	Cell Line	NCI-H460	Homo sapiens	GI50	=	37.0	nM	PMID[496610]
NPT90	Cell Line	DU-145	Homo sapiens	GI50	=	440.0	nM	PMID[496610]
NPT20529	NON-MOLECULAR	NON-PROTEIN TARGET	n.a.	GI50	=	31.0	nM	PMID[496610]
NPT20529	NON-MOLECULAR	NON-PROTEIN TARGET	n.a.	GI50	=	0.038	nM	PMID[496610]

☑ Note for Activity Records:
☉ The quantitative biological activities were primarily integrated from ChEMBL (Version-30) database and were also directly collected from PubMed literature. PubMed PMID was provided as the reference link for each activity record.

Chemically structural similarity: I. Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes 4,3285 NPs with experimentally-derived bioactivity available in NPASS)

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules. Tc lies between [0, 1] where '1' indicates the highest similarity. What is Tanimoto coefficient

● The left chart: Distribution of similarity level between NPC473363 and all remaining natural products in the NPASS database.
● The right table: Most similar natural products (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	389
0.1-0.2	1369
0.2-0.3	6125
0.3-0.4	21823
0.4-0.5	10415
0.5-0.6	2525
0.6-0.7	31
0.7-0.8	2
0.8-0.85	6
0.85-0.9	7
0.9-0.95	2
0.95-1	3

Similarity Score	Similarity Level	Natural Product ID
		NPC

Chemically structural similarity: II. Similar Clinical/Approved Drugs

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules.

● The left chart: Distribution of similarity level between NPC473363 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	233
0.1-0.2	550
0.2-0.3	2129
0.3-0.4	5003
0.4-0.5	1183
0.5-0.6	52
0.6-0.7	0
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
		NPD

Bioactivity similarity: Similar Natural Products in NPASS

Bioactivity similarity was calculated based on bioactivity descriptors of compounds. The bioactivity descriptors were calculated by a recently developed AI algorithm Chemical Checker (CC) [Nature Biotechnology, 38:1087–1096, 2020; Nature Communications, 12:3932, 2021], which evaluated bioactivity similarities at five levels:
☉ A: chemistry similarity;
☉ B: biological targets similarity;
☉ C: networks similarity;
☉ D: cell-based bioactivity similarity;
☉ E: similarity based on clinical data.

Those 5 categories of CC bioactivity descriptors were calculated and then subjected to manifold projection using UMAP algorithm, to project all NPs on a 2-Dimensional space. The current NP was highlighted with a small circle in the 2-D map. Below figures: left-to-right, A-to-E.

A: chemistry similarity

B: biological targets similarity

C: networks similarity

D: cell-based bioactivity similarity

E: similarity based on clinical data