NPASS Compound

Structure

NPC471557 OpenBabel07101718312D 69 81 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 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 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 6.8200 3.3090 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.9540 2.8090 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 5.9540 1.8090 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 24 1 0 0 0 0 2 25 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 26 1 0 0 0 0 10 12 1 0 0 0 0 10 27 1 0 0 0 0 13 26 1 0 0 0 0 13 34 1 0 0 0 0 14 27 1 0 0 0 0 14 35 1 0 0 0 0 15 30 1 0 0 0 0 15 37 1 0 0 0 0 16 31 1 0 0 0 0 16 38 1 0 0 0 0 17 32 2 0 0 0 0 17 41 1 0 0 0 0 18 33 2 0 0 0 0 18 42 1 0 0 0 0 19 36 1 0 0 0 0 19 47 1 0 0 0 0 20 39 1 0 0 0 0 20 45 1 0 0 0 0 21 40 1 0 0 0 0 21 46 1 0 0 0 0 22 45 1 0 0 0 0 22 57 1 0 0 0 0 23 46 1 0 0 0 0 23 58 1 0 0 0 0 24 51 1 6 0 0 0 24 53 1 0 0 0 0 25 52 1 6 0 0 0 25 54 1 0 0 0 0 26 47 1 1 0 0 0 27 48 1 1 0 0 0 28 11 1 6 0 0 0 28 30 1 0 0 0 0 28 32 1 0 0 0 0 29 12 1 6 0 0 0 29 31 1 0 0 0 0 29 33 1 0 0 0 0 30 47 1 1 0 0 0 31 48 1 1 0 0 0 32 49 1 0 0 0 0 33 50 1 0 0 0 0 34 36 2 0 0 0 0 34 56 1 0 0 0 0 35 43 1 0 0 0 0 35 55 2 0 0 0 0 36 55 1 0 0 0 0 37 49 1 1 0 0 0 37 59 1 0 0 0 0 38 50 1 1 0 0 0 38 60 1 0 0 0 0 39 53 1 1 0 0 0 39 61 1 0 0 0 0 40 54 1 1 0 0 0 40 62 1 0 0 0 0 41 51 1 1 0 0 0 41 66 1 0 0 0 0 42 52 1 1 0 0 0 42 67 1 0 0 0 0 43 44 1 0 0 0 0 43 56 2 0 0 0 0 44 48 1 6 0 0 0 44 63 1 0 0 0 0 45 3 1 1 0 0 0 45 68 1 0 0 0 0 46 4 1 1 0 0 0 46 69 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 64 1 6 0 0 0 52 65 1 6 0 0 0 53 66 1 1 0 0 0 53 68 1 0 0 0 0 54 67 1 1 0 0 0 54 69 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	960.53
Volume:	954.39
LogP:	3.069
LogD:	1.035
LogS:	-4.472
# Rotatable Bonds:	2
TPSA:	244.77
# H-Bond Aceptor:	15
# H-Bond Donor:	9
# Rings:	13
# Heavy Atoms:	15

MedChem Properties

QED Drug-Likeness Score:	0.194
Synthetic Accessibility Score:	5.52
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:	-6.18
MDCK Permeability:	6.0211081290617585e-05
Pgp-inhibitor:	0.121
Pgp-substrate:	1.0
Human Intestinal Absorption (HIA):	0.779
20% Bioavailability (F20%):	0.98
30% Bioavailability (F30%):	0.966

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.17
Plasma Protein Binding (PPB):	61.054481506347656%
Volume Distribution (VD):	0.381
Pgp-substrate:	15.358227729797363%

ADMET: Metabolism

CYP1A2-inhibitor:	0.001
CYP1A2-substrate:	0.939
CYP2C19-inhibitor:	0.001
CYP2C19-substrate:	0.674
CYP2C9-inhibitor:	0.004
CYP2C9-substrate:	0.002
CYP2D6-inhibitor:	0.0
CYP2D6-substrate:	0.075
CYP3A4-inhibitor:	0.902
CYP3A4-substrate:	0.496

ADMET: Excretion

Clearance (CL):	3.553
Half-life (T1/2):	0.199

ADMET: Toxicity

hERG Blockers:	0.591
Human Hepatotoxicity (H-HT):	0.988
Drug-inuced Liver Injury (DILI):	0.032
AMES Toxicity:	0.016
Rat Oral Acute Toxicity:	0.987
Maximum Recommended Daily Dose:	0.997
Skin Sensitization:	0.645
Carcinogencity:	0.693
Eye Corrosion:	0.003
Eye Irritation:	0.004
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: NPC471557

Natural Product ID:	NPC471557
*Common Name:**	Cephalostatin 13
IUPAC Name:	n.a.
Synonyms:	Cephalostatin 13
Standard InCHIKey:	ZZWDNFAHBZOHKA-PXTNZQIYSA-N
Standard InCHI:	InChI=1S/C54H76N2O13/c1-24-51(64)41(66-53(24)39(61)20-45(3,22-57)68-53)17-32-28-11-9-26-13-34-36(19-47(26,5)30(28)15-37(59)49(32,51)7)55-35-14-27-10-12-29-31(48(27,6)44(63)43(35)56-34)16-38(60)50(8)33(29)18-42-52(50,65)25(2)54(67-42)40(62)21-46(4,23-58)69-54/h17-18,24-31,37-42,44,57-65H,9-16,19-23H2,1-8H3/t24-,25-,26-,27-,28+,29+,30-,31-,37+,38+,39+,40+,41-,42-,44-,45-,46-,47-,48-,49+,50+,51+,52+,53-,54-/m0/s1
SMILES:	OC[C@]1(C)C[C@H]([C@]2(O1)O[C@@H]1[C@@]([C@@H]2C)(O)[C@@]2(C(=C1)[C@@H]1CC[C@@H]3[C@]([C@H]1C[C@H]2O)(C)Cc1c(C3)nc2c(n1)C[C@H]1[C@@]([C@H]2O)(C)[C@H]2C[C@@H](O)[C@]3(C(=C[C@H]4[C@]3(O)[C@H](C)[C@]3(O4)O[C@](C[C@H]3O)(C)CO)[C@@H]2CC1)C)C)O
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL256953
PubChem CID:	21774831
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000258] Steroids and steroid derivatives [CHEMONTID:0001295] Hydroxysteroids [CHEMONTID:0004158] 1-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	2
GI50	7

Activity Type	# Activity
Cell Line	7
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	=	0.046	ug ml-1	PMID[470723]
NPT4461	Cell Line	Panel (Carcinoma cell lines)	Homo sapiens	GI50	>	1000.0	nM	PMID[470723]
NPT168	Cell Line	P388	Mus musculus	ED50	=	47.9	nM	PMID[470724]
NPT83	Cell Line	MCF7	Homo sapiens	GI50	=	290.0	nM	PMID[470725]
NPT395	Cell Line	SF-268	Homo sapiens	GI50	=	340.0	nM	PMID[470725]
NPT397	Cell Line	NCI-H460	Homo sapiens	GI50	=	370.0	nM	PMID[470725]
NPT90	Cell Line	DU-145	Homo sapiens	GI50	=	1100.0	nM	PMID[470725]
NPT20529	NON-MOLECULAR	NON-PROTEIN TARGET	n.a.	GI50	=	310.0	nM	PMID[470725]
NPT20529	NON-MOLECULAR	NON-PROTEIN TARGET	n.a.	GI50	=	470.0	nM	PMID[470725]

☑ 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 NPC471557 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	419
0.1-0.2	1609
0.2-0.3	6641
0.3-0.4	22205
0.4-0.5	10184
0.5-0.6	1613
0.6-0.7	6
0.7-0.8	2
0.8-0.85	6
0.85-0.9	5
0.9-0.95	6
0.95-1	1

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 NPC471557 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	242
0.1-0.2	606
0.2-0.3	2171
0.3-0.4	4727
0.4-0.5	1331
0.5-0.6	73
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