NPASS Compound

Structure

NPC471558 OpenBabel07101718312D 66 78 0 0 1 0 0 0 0 0999 V2000 -1.2601 0.2601 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -17.9847 -7.8981 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 -17.0947 -6.7991 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -16.2856 -6.2113 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 1.5388 -0.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -14.4210 -6.9271 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 -16.0766 -8.2003 0.0000 C 0 0 0 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 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 -16.9901 -7.7936 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 -15.3721 -6.6180 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 -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 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 1.2601 -2.2601 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -17.3969 -8.7071 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 -15.2676 -7.6126 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 0.0000 -0.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1 26 1 0 0 0 0 6 48 1 0 0 0 0 7 49 1 0 0 0 0 8 10 1 0 0 0 0 8 27 1 0 0 0 0 9 11 1 0 0 0 0 9 28 1 0 0 0 0 12 13 1 0 0 0 0 12 44 1 0 0 0 0 14 27 1 0 0 0 0 14 35 1 0 0 0 0 15 28 1 0 0 0 0 15 36 1 0 0 0 0 16 31 1 0 0 0 0 16 39 1 0 0 0 0 17 32 1 0 0 0 0 17 40 1 0 0 0 0 18 33 2 0 0 0 0 18 42 1 0 0 0 0 19 34 2 0 0 0 0 19 43 1 0 0 0 0 20 37 1 0 0 0 0 20 46 1 0 0 0 0 21 38 1 0 0 0 0 21 47 1 0 0 0 0 22 41 1 0 0 0 0 22 45 1 0 0 0 0 23 50 1 0 0 0 0 23 51 1 0 0 0 0 24 45 1 0 0 0 0 24 56 1 0 0 0 0 25 44 1 0 0 0 0 25 63 1 0 0 0 0 26 52 1 6 0 0 0 26 53 1 0 0 0 0 27 46 1 1 0 0 0 28 47 1 1 0 0 0 29 10 1 6 0 0 0 29 31 1 0 0 0 0 29 33 1 0 0 0 0 30 11 1 6 0 0 0 30 32 1 0 0 0 0 30 34 1 0 0 0 0 31 46 1 1 0 0 0 32 47 1 1 0 0 0 33 48 1 0 0 0 0 34 49 1 0 0 0 0 35 37 2 0 0 0 0 35 55 1 0 0 0 0 36 38 1 0 0 0 0 36 54 2 0 0 0 0 37 54 1 0 0 0 0 38 55 2 0 0 0 0 39 48 1 1 0 0 0 39 57 1 0 0 0 0 40 49 1 1 0 0 0 40 58 1 0 0 0 0 41 53 1 1 0 0 0 41 59 1 0 0 0 0 42 51 1 1 0 0 0 42 64 1 0 0 0 0 43 52 1 1 0 0 0 43 65 1 0 0 0 0 44 2 1 6 0 0 0 44 60 1 0 0 0 0 45 3 1 1 0 0 0 45 66 1 0 0 0 0 46 4 1 1 0 0 0 47 5 1 1 0 0 0 48 51 1 6 0 0 0 49 52 1 6 0 0 0 50 13 1 1 0 0 0 50 63 1 0 0 0 0 50 64 1 0 0 0 0 51 61 1 6 0 0 0 52 62 1 6 0 0 0 53 65 1 1 0 0 0 53 66 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	914.53
Volume:	919.513
LogP:	4.145
LogD:	2.349
LogS:	-4.654
# Rotatable Bonds:	1
TPSA:	204.31
# H-Bond Aceptor:	13
# H-Bond Donor:	7
# Rings:	13
# Heavy Atoms:	13

MedChem Properties

QED Drug-Likeness Score:	0.198
Synthetic Accessibility Score:	7.842
Fsp3:	0.849
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:	-5.754
MDCK Permeability:	1.7095451767090708e-05
Pgp-inhibitor:	0.315
Pgp-substrate:	1.0
Human Intestinal Absorption (HIA):	0.726
20% Bioavailability (F20%):	0.997
30% Bioavailability (F30%):	0.681

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.158
Plasma Protein Binding (PPB):	62.38581848144531%
Volume Distribution (VD):	0.529
Pgp-substrate:	14.949848175048828%

ADMET: Metabolism

CYP1A2-inhibitor:	0.001
CYP1A2-substrate:	0.97
CYP2C19-inhibitor:	0.009
CYP2C19-substrate:	0.742
CYP2C9-inhibitor:	0.04
CYP2C9-substrate:	0.002
CYP2D6-inhibitor:	0.001
CYP2D6-substrate:	0.04
CYP3A4-inhibitor:	0.981
CYP3A4-substrate:	0.829

ADMET: Excretion

Clearance (CL):	6.849
Half-life (T1/2):	0.196

ADMET: Toxicity

hERG Blockers:	0.871
Human Hepatotoxicity (H-HT):	0.898
Drug-inuced Liver Injury (DILI):	0.04
AMES Toxicity:	0.015
Rat Oral Acute Toxicity:	0.995
Maximum Recommended Daily Dose:	0.997
Skin Sensitization:	0.829
Carcinogencity:	0.924
Eye Corrosion:	0.003
Eye Irritation:	0.004
Respiratory Toxicity:	0.992

Download Data

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

Natural Product: NPC471558

Natural Product ID:	NPC471558
*Common Name:**	Cephalostatin 7
IUPAC Name:	n.a.
Synonyms:	Cephalostatin 7
Standard InCHIKey:	MQQWDJVBMQSXMK-NTTLTFHJSA-N
Standard InCHI:	InChI=1S/C53H74N2O11/c1-26-52(62)43(65-53(26)41(59)22-45(3,24-56)66-53)19-34-30-11-9-28-15-36-38(21-47(28,5)32(30)17-40(58)49(34,52)7)55-35-14-27-8-10-29-31(46(27,4)20-37(35)54-36)16-39(57)48(6)33(29)18-42-51(48,61)23-50(64-42)13-12-44(2,60)25-63-50/h18-19,26-32,39-43,56-62H,8-17,20-25H2,1-7H3/t26-,27-,28-,29+,30+,31-,32-,39+,40+,41+,42-,43-,44-,45-,46-,47-,48+,49+,50+,51+,52+,53-/m0/s1
SMILES:	CC1C2(C(CC(O2)(C)CO)O)OC3C1(C4(C(CC5C(C4=C3)CCC6C5(CC7=NC8=C(CC9(C(C8)CCC1C9CC(C2(C1=CC1C2(CC2(O1)CCC(CO2)(C)O)O)C)O)C)N=C7C6)C)O)C)O
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL256973
PubChem CID:	44448143
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	8
GI50	27

Activity Type	# Activity
Cell Line	29
NON-MOLECULAR	4
Organism	2

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT81	Cell Line	A549	Homo sapiens	ED50	=	0.00003	nM	PMID[529812]
NPT139	Cell Line	HT-29	Homo sapiens	ED50	=	30.0	nM	PMID[529812]
NPT376	Cell Line	A498	Homo sapiens	ED50	=	0.00055	nM	PMID[529812]
NPT306	Cell Line	PC-3	Homo sapiens	ED50	=	0.0021	nM	PMID[529812]
NPT168	Cell Line	P388	Mus musculus	ED50	=	0.0001	nM	PMID[529812]
NPT116	Cell Line	HL-60	Homo sapiens	GI50	=	25.0	nM	PMID[529812]
NPT81	Cell Line	A549	Homo sapiens	GI50	=	138.0	nM	PMID[529812]
NPT139	Cell Line	HT-29	Homo sapiens	GI50	=	271.0	nM	PMID[529812]
NPT399	Cell Line	SF-295	Homo sapiens	GI50	=	11.0	nM	PMID[529812]
NPT83	Cell Line	MCF7	Homo sapiens	GI50	=	27.0	nM	PMID[529812]
NPT458	Cell Line	IGROV-1	Homo sapiens	GI50	=	480.0	nM	PMID[529812]
NPT390	Cell Line	LOX IMVI	Homo sapiens	GI50	=	37.0	nM	PMID[529812]
NPT376	Cell Line	A498	Homo sapiens	GI50	=	31.0	nM	PMID[529812]
NPT406	Cell Line	RXF 393	Homo sapiens	GI50	=	7.9	nM	PMID[529812]
NPT306	Cell Line	PC-3	Homo sapiens	GI50	=	23.0	nM	PMID[529812]
NPT517	Cell Line	Panel NCI-60 (60 carcinoma cell lines)	Homo sapiens	GI50	=	50.0	nM	PMID[529812]
NPT4859	Cell Line	NCI		GI50	=	16.0	nM	PMID[529812]
NPT379	Cell Line	HOP-62	Homo sapiens	GI50	<	0.1	nM	PMID[529813]
NPT116	Cell Line	HL-60	Homo sapiens	GI50	<	0.1	nM	PMID[529813]
NPT404	Cell Line	CCRF-CEM	Homo sapiens	GI50	<	0.1	nM	PMID[529813]
NPT399	Cell Line	SF-295	Homo sapiens	GI50	<	0.1	nM	PMID[529813]
NPT380	Cell Line	U-251	Homo sapiens	GI50	<	0.1	nM	PMID[529813]
NPT406	Cell Line	RXF 393	Homo sapiens	GI50	<	0.1	nM	PMID[529813]
NPT572	Cell Line	DMS-273	Homo sapiens	GI50	<	0.1	nM	PMID[529813]
NPT168	Cell Line	P388	Mus musculus	GI50	<	0.1	nM	PMID[529813]
NPT83	Cell Line	MCF7	Homo sapiens	GI50	=	50.0	nM	PMID[529814]
NPT395	Cell Line	SF-268	Homo sapiens	GI50	=	110.0	nM	PMID[529814]
NPT397	Cell Line	NCI-H460	Homo sapiens	GI50	=	8.2	nM	PMID[529814]
NPT90	Cell Line	DU-145	Homo sapiens	GI50	=	470.0	nM	PMID[529814]
NPT605	Organism	Homo sapiens	Homo sapiens	ED50	=	38.0	nM	PMID[529812]
NPT20529	NON-MOLECULAR	NON-PROTEIN TARGET	n.a.	ED50	=	0.41	nM	PMID[529812]
NPT605	Organism	Homo sapiens	Homo sapiens	ED50	=	0.052	nM	PMID[529812]
NPT20529	NON-MOLECULAR	NON-PROTEIN TARGET	n.a.	GI50	<	0.1	nM	PMID[529813]
NPT20529	NON-MOLECULAR	NON-PROTEIN TARGET	n.a.	GI50	=	5.0	nM	PMID[529814]
NPT20529	NON-MOLECULAR	NON-PROTEIN TARGET	n.a.	GI50	=	48.0	nM	PMID[529814]

☑ 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 NPC471558 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	377
0.1-0.2	1331
0.2-0.3	5713
0.3-0.4	21596
0.4-0.5	10752
0.5-0.6	2839
0.6-0.7	69
0.7-0.8	2
0.8-0.85	3
0.85-0.9	6
0.9-0.95	6
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 NPC471558 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	224
0.1-0.2	542
0.2-0.3	2028
0.3-0.4	4992
0.4-0.5	1304
0.5-0.6	60
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