NPASS Compound

Structure

CID253456 OpenBabel06191716052D 38 44 0 0 1 0 0 0 0 0999 V2000 3.4276 -1.9789 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2665 3.4189 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0005 3.9213 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8487 4.4116 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5466 2.4507 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2445 5.3915 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3958 2.9410 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3958 5.8815 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6984 -1.9611 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.5835 3.0742 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8494 2.4509 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8489 1.4703 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.7487 4.6505 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6974 1.9604 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5476 -1.4708 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -5.0935 3.9224 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0005 2.9407 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.2450 4.4119 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.6979 2.9407 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.6979 3.9213 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 0.8492 1.4709 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.0000 0.9806 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 0.8492 -1.4708 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -6.5416 3.2781 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6984 0.0000 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.3958 3.9216 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.8487 2.4504 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.5471 4.4116 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 0.8492 -0.4903 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.4936 1.0017 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.0308 -1.9789 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.2698 2.6229 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.6811 4.9116 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.0308 -0.9984 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.6437 4.2523 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.5476 -0.4902 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.6984 0.9806 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 2 26 1 0 0 0 0 3 4 1 0 0 0 0 3 17 1 0 0 0 0 4 20 1 0 0 0 0 5 7 1 0 0 0 0 5 19 1 0 0 0 0 6 8 1 0 0 0 0 6 18 1 0 0 0 0 7 26 1 0 0 0 0 8 28 1 0 0 0 0 9 15 1 0 0 0 0 9 23 1 0 0 0 0 10 16 2 0 0 0 0 10 24 1 0 0 0 0 11 17 1 0 0 0 0 12 27 1 0 0 0 0 13 16 1 0 0 0 0 13 35 1 0 0 0 0 14 30 2 0 0 0 0 15 1 1 6 0 0 0 15 36 1 0 0 0 0 16 18 1 0 0 0 0 17 27 1 1 0 0 0 18 26 1 1 0 0 0 19 20 1 0 0 0 0 19 27 1 1 0 0 0 20 28 1 6 0 0 0 21 11 1 1 0 0 0 21 22 1 0 0 0 0 21 37 1 0 0 0 0 22 12 1 6 0 0 0 22 38 1 0 0 0 0 23 29 1 6 0 0 0 23 31 1 0 0 0 0 24 32 2 0 0 0 0 24 35 1 0 0 0 0 25 29 1 6 0 0 0 25 36 1 0 0 0 0 25 37 1 0 0 0 0 26 28 1 1 0 0 0 27 14 1 1 0 0 0 28 33 1 1 0 0 0 29 34 1 1 0 0 0 29 38 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	532.27
Volume:	521.447
LogP:	3.311
LogD:	2.414
LogS:	-3.675
# Rotatable Bonds:	2
TPSA:	138.82
# H-Bond Aceptor:	9
# H-Bond Donor:	4
# Rings:	7
# Heavy Atoms:	9

MedChem Properties

QED Drug-Likeness Score:	0.334
Synthetic Accessibility Score:	5.755
Fsp3:	0.828
Lipinski Rule-of-5:	Accepted
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:	-5.32
MDCK Permeability:	3.3702290238579735e-05
Pgp-inhibitor:	0.732
Pgp-substrate:	0.997
Human Intestinal Absorption (HIA):	0.152
20% Bioavailability (F20%):	0.909
30% Bioavailability (F30%):	0.817

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.956
Plasma Protein Binding (PPB):	77.8641128540039%
Volume Distribution (VD):	1.621
Pgp-substrate:	11.558051109313965%

ADMET: Metabolism

CYP1A2-inhibitor:	0.007
CYP1A2-substrate:	0.778
CYP2C19-inhibitor:	0.01
CYP2C19-substrate:	0.208
CYP2C9-inhibitor:	0.023
CYP2C9-substrate:	0.059
CYP2D6-inhibitor:	0.009
CYP2D6-substrate:	0.162
CYP3A4-inhibitor:	0.694
CYP3A4-substrate:	0.256

ADMET: Excretion

Clearance (CL):	5.396
Half-life (T1/2):	0.28

ADMET: Toxicity

hERG Blockers:	0.44
Human Hepatotoxicity (H-HT):	0.3
Drug-inuced Liver Injury (DILI):	0.184
AMES Toxicity:	0.362
Rat Oral Acute Toxicity:	0.908
Maximum Recommended Daily Dose:	0.969
Skin Sensitization:	0.854
Carcinogencity:	0.768
Eye Corrosion:	0.003
Eye Irritation:	0.012
Respiratory Toxicity:	0.97

Download Data

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

Natural Product: NPC253456

Natural Product ID:	NPC253456
*Common Name:**	Calotropin
IUPAC Name:	n.a.
Synonyms:	Calotropin
Standard InCHIKey:	OWPWFVVPBYFKBG-NYVHBPEFSA-N
Standard InCHI:	InChI=1S/C29H40O9/c1-15-9-23(31)29(34)25(36-15)37-21-11-17-3-4-20-19(27(17,14-30)12-22(21)38-29)5-7-26(2)18(6-8-28(20,26)33)16-10-24(32)35-13-16/h10,14-15,17-23,25,31,33-34H,3-9,11-13H2,1-2H3/t15-,17+,18-,19+,20-,21-,22-,23+,25+,26-,27-,28+,29+/m1/s1
SMILES:	C[C@@H]1C[C@@H]([C@]2([C@@H](O1)O[C@@H]1C[C@@H]3CC[C@@H]4[C@H](CC[C@]5(C)[C@H](CC[C@]45O)C4=CC(=O)OC4)[C@]3(C[C@H]1O2)C=O)O)O
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL495949
PubChem CID:	16142
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000258] Steroids and steroid derivatives [CHEMONTID:0001125] Steroid lactones [CHEMONTID:0001555] Cardenolides and derivatives [CHEMONTID:0001559] Cardenolide glycosides and derivatives

*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
NPO9165	Asclepias curassavica	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[16252914]
NPO30295	Calotropis gigantea	Species	Apocynaceae	Eukaryota	leaves	n.a.	n.a.	PMID[16933890]
NPO30295	Calotropis gigantea	Species	Apocynaceae	Eukaryota	n.a.	root	n.a.	PMID[19052526]
NPO9165	Asclepias curassavica	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[19251412]
NPO30295	Calotropis gigantea	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[28817274]
NPO30295	Calotropis gigantea	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[31967821]
NPO30295	Calotropis gigantea	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[32649211]
NPO30295	Calotropis gigantea	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[9548837]
NPO9165	Asclepias curassavica	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO9165	Asclepias curassavica	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO3369	Anemone narcissiflora	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO2175	Hyperbaena columbica	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO8349	Uga sinensis	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[UNPD]
NPO26375	Viburnum grandifolium	Species	Adoxaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO9165	Asclepias curassavica	Species	Apocynaceae	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
EC50	1
GI50	60
IC50	17
Others	2

Activity Type	# Activity
Cell Line	75
NON-MOLECULAR	1
Others	3
SINGLE PROTEIN	1

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT65	Cell Line	HepG2	Homo sapiens	IC50	=	40.0	nM	PMID[544614]
NPT80	Cell Line	Raji	Homo sapiens	IC50	=	20.0	nM	PMID[544614]
NPT81	Cell Line	A549	Homo sapiens	IC50	=	0.02	ug.mL-1	PMID[544615]
NPT82	Cell Line	MDA-MB-231	Homo sapiens	IC50	=	0.16	ug.mL-1	PMID[544615]
NPT83	Cell Line	MCF7	Homo sapiens	IC50	=	0.08	ug.mL-1	PMID[544615]
NPT65	Cell Line	HepG2	Homo sapiens	IC50	=	0.11	ug.mL-1	PMID[544615]
NPT91	Cell Line	KB	Homo sapiens	IC50	=	0.015	ug.mL-1	PMID[544615]
NPT91	Cell Line	KB	Homo sapiens	IC50	=	62.0	nM	PMID[544616]
NPT639	Cell Line	NCI-H187	Homo sapiens	IC50	=	471.0	nM	PMID[544616]
NPT368	Cell Line	SN12C	Homo sapiens	GI50	n.a.	20.18	nM	PMID[544617]
NPT367	Cell Line	MDA-N	Homo sapiens	GI50	n.a.	69.18	nM	PMID[544617]
NPT369	Cell Line	ACHN	Homo sapiens	GI50	n.a.	18.75	nM	PMID[544617]
NPT370	Cell Line	NCI-H23	Homo sapiens	GI50	n.a.	18.75	nM	PMID[544617]
NPT371	Cell Line	UO-31	Homo sapiens	GI50	n.a.	58.34	nM	PMID[544617]
NPT372	Cell Line	HOP-92	Homo sapiens	GI50	n.a.	54.45	nM	PMID[544617]
NPT90	Cell Line	DU-145	Homo sapiens	GI50	n.a.	13.4	nM	PMID[544617]
NPT116	Cell Line	HL-60	Homo sapiens	GI50	n.a.	39.72	nM	PMID[544617]
NPT373	Cell Line	SK-MEL-5	Homo sapiens	GI50	n.a.	27.8	nM	PMID[544617]
NPT374	Cell Line	SF-539	Homo sapiens	GI50	n.a.	21.18	nM	PMID[544617]
NPT375	Cell Line	Malme-3M	Homo sapiens	GI50	n.a.	16.67	nM	PMID[544617]
NPT111	Cell Line	K562	Homo sapiens	GI50	n.a.	36.48	nM	PMID[544617]
NPT376	Cell Line	A498	Homo sapiens	GI50	n.a.	53.09	nM	PMID[544617]
NPT377	Cell Line	OVCAR-3	Homo sapiens	GI50	n.a.	18.2	nM	PMID[544617]
NPT112	Cell Line	MOLT-4	Homo sapiens	GI50	n.a.	16.26	nM	PMID[544617]
NPT378	Cell Line	NCI/ADR-RES	Homo sapiens	GI50	n.a.	20.56	nM	PMID[544617]
NPT379	Cell Line	HOP-62	Homo sapiens	GI50	n.a.	24.43	nM	PMID[544617]
NPT380	Cell Line	U-251	Homo sapiens	GI50	n.a.	33.96	nM	PMID[544617]
NPT381	Cell Line	OVCAR-8	Homo sapiens	GI50	n.a.	34.75	nM	PMID[544617]
NPT382	Cell Line	OVCAR-5	Homo sapiens	GI50	n.a.	126.18	nM	PMID[544617]
NPT82	Cell Line	MDA-MB-231	Homo sapiens	GI50	n.a.	221.31	nM	PMID[544617]
NPT383	Cell Line	SNB-19	Homo sapiens	GI50	n.a.	82.99	nM	PMID[544617]
NPT385	Cell Line	SR	Homo sapiens	GI50	n.a.	18.11	nM	PMID[544617]
NPT384	Cell Line	TK-10	Homo sapiens	GI50	n.a.	25.41	nM	PMID[544617]
NPT323	Cell Line	SW-620	Homo sapiens	GI50	n.a.	24.66	nM	PMID[544617]
NPT386	Cell Line	KM12	Homo sapiens	GI50	n.a.	80.91	nM	PMID[544617]
NPT455	Cell Line	NCI-H522	Homo sapiens	GI50	n.a.	16.18	nM	PMID[544617]
NPT387	Cell Line	M14	Homo sapiens	GI50	n.a.	65.01	nM	PMID[544617]
NPT388	Cell Line	NCI-H322M	Homo sapiens	GI50	n.a.	28.18	nM	PMID[544617]
NPT389	Cell Line	RPMI-8226	Homo sapiens	GI50	n.a.	24.55	nM	PMID[544617]
NPT456	Cell Line	OVCAR-4	Homo sapiens	GI50	n.a.	17.91	nM	PMID[544617]
NPT390	Cell Line	LOX IMVI	Homo sapiens	GI50	n.a.	23.12	nM	PMID[544617]
NPT457	Cell Line	BT-549	Homo sapiens	GI50	n.a.	23.12	nM	PMID[544617]
NPT147	Cell Line	SK-MEL-2	Homo sapiens	GI50	n.a.	43.65	nM	PMID[544617]
NPT391	Cell Line	HCC 2998	Homo sapiens	GI50	n.a.	59.29	nM	PMID[544617]
NPT81	Cell Line	A549	Homo sapiens	GI50	n.a.	14.03	nM	PMID[544617]
NPT392	Cell Line	SNB-75	Homo sapiens	GI50	n.a.	68.87	nM	PMID[544617]
NPT148	Cell Line	HCT-15	Homo sapiens	GI50	n.a.	32.66	nM	PMID[544617]
NPT393	Cell Line	HCT-116	Homo sapiens	GI50	n.a.	19.32	nM	PMID[544617]
NPT394	Cell Line	EKVX	Homo sapiens	GI50	n.a.	17.82	nM	PMID[544617]
NPT395	Cell Line	SF-268	Homo sapiens	GI50	n.a.	40.64	nM	PMID[544617]
NPT306	Cell Line	PC-3	Homo sapiens	GI50	n.a.	23.44	nM	PMID[544617]
NPT83	Cell Line	MCF7	Homo sapiens	GI50	n.a.	23.77	nM	PMID[544617]
NPT146	Cell Line	SK-OV-3	Homo sapiens	GI50	n.a.	35.08	nM	PMID[544617]
NPT397	Cell Line	NCI-H460	Homo sapiens	GI50	n.a.	18.66	nM	PMID[544617]
NPT396	Cell Line	T47D	Homo sapiens	GI50	n.a.	30.27	nM	PMID[544617]
NPT308	Cell Line	CAKI-1	Homo sapiens	GI50	n.a.	22.96	nM	PMID[544617]
NPT398	Cell Line	UACC-62	Homo sapiens	GI50	n.a.	71.78	nM	PMID[544617]
NPT399	Cell Line	SF-295	Homo sapiens	GI50	n.a.	37.24	nM	PMID[544617]
NPT400	Cell Line	MDA-MB-435	Homo sapiens	GI50	n.a.	67.45	nM	PMID[544617]
NPT458	Cell Line	IGROV-1	Homo sapiens	GI50	n.a.	20.94	nM	PMID[544617]
NPT401	Cell Line	786-0	Homo sapiens	GI50	n.a.	15.56	nM	PMID[544617]
NPT402	Cell Line	Hs-578T	Homo sapiens	GI50	n.a.	26.3	nM	PMID[544617]
NPT403	Cell Line	UACC-257	Homo sapiens	GI50	n.a.	59.16	nM	PMID[544617]
NPT404	Cell Line	CCRF-CEM	Homo sapiens	GI50	n.a.	17.5	nM	PMID[544617]
NPT139	Cell Line	HT-29	Homo sapiens	GI50	n.a.	42.46	nM	PMID[544617]
NPT405	Cell Line	NCI-H226	Homo sapiens	GI50	n.a.	81.47	nM	PMID[544617]
NPT170	Cell Line	SK-MEL-28	Homo sapiens	GI50	n.a.	111.94	nM	PMID[544617]
NPT406	Cell Line	RXF 393	Homo sapiens	GI50	n.a.	17.62	nM	PMID[544617]
NPT407	Cell Line	COLO 205	Homo sapiens	GI50	n.a.	72.61	nM	PMID[544617]
NPT90	Cell Line	DU-145	Homo sapiens	IC50	=	30.0	nM	PMID[544619]
NPT461	Cell Line	PANC-1	Homo sapiens	IC50	>	10000.0	nM	PMID[544620]
NPT165	Cell Line	HeLa	Homo sapiens	IC50	>	10000.0	nM	PMID[544620]
NPT457	Cell Line	BT-549	Homo sapiens	IC50	=	30.0	nM	PMID[544621]
NPT402	Cell Line	Hs-578T	Homo sapiens	IC50	=	60.0	nM	PMID[544621]
NPT82	Cell Line	MDA-MB-231	Homo sapiens	IC50	=	440.0	nM	PMID[544621]
NPT20529	NON-MOLECULAR	NON-PROTEIN TARGET	n.a.	IC50	=	41.3	nM	PMID[544616]
NPT25172	SINGLE PROTEIN	Neurogenic locus notch homolog protein 1	Homo sapiens	IC50	=	800.0	nM	PMID[544618]
NPT2	Others	Unspecified		Ratio IC50	=	15.0	n.a.	PMID[544621]
NPT2	Others	Unspecified		EC50	=	360.0	nM	PMID[544621]
NPT2	Others	Unspecified		FC	=	2.0	n.a.	PMID[544621]

☑ 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 NPC253456 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	306
0.1-0.2	1794
0.2-0.3	5080
0.3-0.4	9374
0.4-0.5	11128
0.5-0.6	7051
0.6-0.7	4829
0.7-0.8	2167
0.8-0.85	665
0.85-0.9	202
0.9-0.95	56
0.95-1	45

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC159338
1.0	High Similarity	NPC16569
0.9917	High Similarity	NPC19124
0.9917	High Similarity	NPC42670
0.9917	High Similarity	NPC93416
0.9916	High Similarity	NPC91
0.9835	High Similarity	NPC104585
0.9835	High Similarity	NPC298783
0.9835	High Similarity	NPC477709
0.9835	High Similarity	NPC157817
0.9835	High Similarity	NPC225385
0.9835	High Similarity	NPC476221
0.975	High Similarity	NPC140092
0.975	High Similarity	NPC329986
0.975	High Similarity	NPC232785
0.975	High Similarity	NPC125077
0.975	High Similarity	NPC276838
0.975	High Similarity	NPC188234
0.9672	High Similarity	NPC142756
0.9664	High Similarity	NPC250556
0.9664	High Similarity	NPC469750
0.9583	High Similarity	NPC471356
0.9583	High Similarity	NPC179412
0.9583	High Similarity	NPC329784
0.9583	High Similarity	NPC240070
0.9512	High Similarity	NPC247190
0.9512	High Similarity	NPC469749
0.9512	High Similarity	NPC146857
0.9512	High Similarity	NPC116075
0.9512	High Similarity	NPC32793
0.9496	High Similarity	NPC27363
0.944	High Similarity	NPC59288
0.9435	High Similarity	NPC329636
0.9426	High Similarity	NPC471361
0.9426	High Similarity	NPC471359
0.9426	High Similarity	NPC10823
0.9426	High Similarity	NPC251866
0.9426	High Similarity	NPC70542
0.9426	High Similarity	NPC180079
0.9426	High Similarity	NPC89514
0.9426	High Similarity	NPC471352
0.9426	High Similarity	NPC469751
0.9426	High Similarity	NPC197707
0.9426	High Similarity	NPC469755
0.9426	High Similarity	NPC219085
0.9426	High Similarity	NPC9499
0.9426	High Similarity	NPC469752
0.9426	High Similarity	NPC86159
0.9426	High Similarity	NPC284406
0.9426	High Similarity	NPC17896
0.9426	High Similarity	NPC469753
0.9426	High Similarity	NPC6108
0.9426	High Similarity	NPC471358
0.9426	High Similarity	NPC469754
0.9426	High Similarity	NPC471360
0.936	High Similarity	NPC194716
0.936	High Similarity	NPC171619
0.9286	High Similarity	NPC329675
0.9262	High Similarity	NPC469757
0.9262	High Similarity	NPC471357
0.9262	High Similarity	NPC146456
0.9262	High Similarity	NPC117702
0.92	High Similarity	NPC88668
0.916	High Similarity	NPC329905
0.9083	High Similarity	NPC475136
0.9083	High Similarity	NPC474466
0.9032	High Similarity	NPC311534
0.9	High Similarity	NPC30483
0.9	High Similarity	NPC292467
0.9	High Similarity	NPC236973
0.9	High Similarity	NPC469756
0.9	High Similarity	NPC32177
0.9	High Similarity	NPC55532
0.9	High Similarity	NPC470897
0.8992	High Similarity	NPC152615
0.8926	High Similarity	NPC475629
0.8926	High Similarity	NPC470312
0.8926	High Similarity	NPC475556
0.8926	High Similarity	NPC72260
0.8908	High Similarity	NPC199428
0.8908	High Similarity	NPC193382
0.8908	High Similarity	NPC5311
0.8908	High Similarity	NPC310341
0.8908	High Similarity	NPC196931
0.8908	High Similarity	NPC99620
0.8852	High Similarity	NPC314535
0.8852	High Similarity	NPC474908
0.8852	High Similarity	NPC173555
0.8852	High Similarity	NPC40749
0.8852	High Similarity	NPC120390
0.8852	High Similarity	NPC475590
0.8852	High Similarity	NPC231518
0.8852	High Similarity	NPC475419
0.8852	High Similarity	NPC475219
0.8837	High Similarity	NPC62172
0.8837	High Similarity	NPC289700
0.8833	High Similarity	NPC27507
0.8833	High Similarity	NPC471351
0.8833	High Similarity	NPC93883
0.8833	High Similarity	NPC474418
0.8833	High Similarity	NPC471354
0.8833	High Similarity	NPC34390
0.8833	High Similarity	NPC244402
0.8833	High Similarity	NPC77319
0.8833	High Similarity	NPC84987
0.8833	High Similarity	NPC158344
0.8833	High Similarity	NPC157376
0.8833	High Similarity	NPC471353
0.8833	High Similarity	NPC473852
0.8833	High Similarity	NPC309034
0.8833	High Similarity	NPC243196
0.8833	High Similarity	NPC142066
0.8833	High Similarity	NPC196429
0.8833	High Similarity	NPC471355
0.8833	High Similarity	NPC87250
0.8833	High Similarity	NPC99728
0.8833	High Similarity	NPC50305
0.8824	High Similarity	NPC471633
0.8824	High Similarity	NPC31354
0.8824	High Similarity	NPC69576
0.8824	High Similarity	NPC84949
0.8819	High Similarity	NPC471855
0.8819	High Similarity	NPC155529
0.878	High Similarity	NPC193893
0.878	High Similarity	NPC474423
0.878	High Similarity	NPC28532
0.878	High Similarity	NPC264336
0.878	High Similarity	NPC74259
0.876	High Similarity	NPC83287
0.876	High Similarity	NPC218093
0.874	High Similarity	NPC173347
0.873	High Similarity	NPC114306
0.873	High Similarity	NPC477490
0.871	High Similarity	NPC117445
0.871	High Similarity	NPC208193
0.871	High Similarity	NPC308262
0.8702	High Similarity	NPC75616
0.8702	High Similarity	NPC290746
0.8702	High Similarity	NPC79250
0.8692	High Similarity	NPC127656
0.8689	High Similarity	NPC29639
0.8689	High Similarity	NPC81222
0.8689	High Similarity	NPC44899
0.8689	High Similarity	NPC291820
0.8689	High Similarity	NPC304260
0.8689	High Similarity	NPC5883
0.8678	High Similarity	NPC290693
0.8678	High Similarity	NPC203862
0.8661	High Similarity	NPC471407
0.8618	High Similarity	NPC107607
0.8615	High Similarity	NPC158350
0.8595	High Similarity	NPC138372
0.8595	High Similarity	NPC106228
0.8594	High Similarity	NPC477493
0.8538	High Similarity	NPC248703
0.8537	High Similarity	NPC122971
0.8537	High Similarity	NPC19028
0.8537	High Similarity	NPC477071
0.8537	High Similarity	NPC9674
0.8527	High Similarity	NPC477195
0.8525	High Similarity	NPC474483
0.8516	High Similarity	NPC476966
0.8516	High Similarity	NPC231529
0.8512	High Similarity	NPC477580
0.8512	High Similarity	NPC178289
0.848	Intermediate Similarity	NPC115349
0.8468	Intermediate Similarity	NPC476127
0.8468	Intermediate Similarity	NPC476150
0.8468	Intermediate Similarity	NPC281840
0.8455	Intermediate Similarity	NPC45475
0.8443	Intermediate Similarity	NPC72772
0.8443	Intermediate Similarity	NPC471816
0.8443	Intermediate Similarity	NPC469794
0.8438	Intermediate Similarity	NPC69273
0.8438	Intermediate Similarity	NPC168899
0.8438	Intermediate Similarity	NPC293623
0.8425	Intermediate Similarity	NPC174367
0.8425	Intermediate Similarity	NPC47113
0.8413	Intermediate Similarity	NPC41129
0.8397	Intermediate Similarity	NPC476778
0.8397	Intermediate Similarity	NPC476777
0.8387	Intermediate Similarity	NPC475041
0.8385	Intermediate Similarity	NPC478154
0.8374	Intermediate Similarity	NPC477252
0.8374	Intermediate Similarity	NPC473405
0.8372	Intermediate Similarity	NPC477196
0.8361	Intermediate Similarity	NPC472274
0.8359	Intermediate Similarity	NPC470780
0.8359	Intermediate Similarity	NPC287423
0.8346	Intermediate Similarity	NPC318135
0.8346	Intermediate Similarity	NPC473505
0.8333	Intermediate Similarity	NPC110700
0.8333	Intermediate Similarity	NPC269642
0.8333	Intermediate Similarity	NPC279915
0.8321	Intermediate Similarity	NPC476779
0.8321	Intermediate Similarity	NPC316915
0.8321	Intermediate Similarity	NPC478151
0.832	Intermediate Similarity	NPC108072
0.832	Intermediate Similarity	NPC472004
0.832	Intermediate Similarity	NPC471406

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 NPC253456 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	263
0.1-0.2	1978
0.2-0.3	3978
0.3-0.4	1931
0.4-0.5	522
0.5-0.6	281
0.6-0.7	138
0.7-0.8	44
0.8-0.85	2
0.85-0.9	9
0.9-0.95	3
0.95-1	1

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.9664	High Similarity	NPD7507	Approved
0.9426	High Similarity	NPD7319	Approved
0.8926	High Similarity	NPD8294	Approved
0.8926	High Similarity	NPD8377	Approved
0.8852	High Similarity	NPD8380	Approved
0.8852	High Similarity	NPD8033	Approved
0.8852	High Similarity	NPD8296	Approved
0.8852	High Similarity	NPD8379	Approved
0.8852	High Similarity	NPD8335	Approved
0.8852	High Similarity	NPD8378	Approved
0.8843	High Similarity	NPD7516	Approved
0.876	High Similarity	NPD7328	Approved
0.876	High Similarity	NPD7327	Approved
0.8279	Intermediate Similarity	NPD8133	Approved
0.8167	Intermediate Similarity	NPD6686	Approved
0.811	Intermediate Similarity	NPD7503	Approved
0.8015	Intermediate Similarity	NPD7736	Approved
0.7984	Intermediate Similarity	NPD8328	Phase 3
0.7934	Intermediate Similarity	NPD6412	Phase 2
0.7803	Intermediate Similarity	NPD8293	Discontinued
0.7769	Intermediate Similarity	NPD6370	Approved
0.7661	Intermediate Similarity	NPD8132	Clinical (unspecified phase)
0.7656	Intermediate Similarity	NPD8295	Clinical (unspecified phase)
0.7652	Intermediate Similarity	NPD7492	Approved
0.7647	Intermediate Similarity	NPD7638	Approved
0.7619	Intermediate Similarity	NPD6882	Approved
0.7615	Intermediate Similarity	NPD6054	Approved
0.7615	Intermediate Similarity	NPD6059	Approved
0.7594	Intermediate Similarity	NPD6616	Approved
0.7583	Intermediate Similarity	NPD7640	Approved
0.7583	Intermediate Similarity	NPD7639	Approved
0.7557	Intermediate Similarity	NPD8513	Phase 3
0.7557	Intermediate Similarity	NPD8517	Approved
0.7557	Intermediate Similarity	NPD8515	Approved
0.7557	Intermediate Similarity	NPD8516	Approved
0.7537	Intermediate Similarity	NPD7078	Approved
0.752	Intermediate Similarity	NPD6372	Approved
0.752	Intermediate Similarity	NPD6373	Approved
0.7519	Intermediate Similarity	NPD6009	Approved
0.7481	Intermediate Similarity	NPD6319	Approved
0.748	Intermediate Similarity	NPD8170	Clinical (unspecified phase)
0.748	Intermediate Similarity	NPD8297	Approved
0.7448	Intermediate Similarity	NPD7625	Phase 1
0.744	Intermediate Similarity	NPD7320	Approved
0.7424	Intermediate Similarity	NPD6015	Approved
0.7424	Intermediate Similarity	NPD6016	Approved
0.7422	Intermediate Similarity	NPD4632	Approved
0.7419	Intermediate Similarity	NPD6675	Approved
0.7419	Intermediate Similarity	NPD7128	Approved
0.7419	Intermediate Similarity	NPD6402	Approved
0.7419	Intermediate Similarity	NPD5739	Approved
0.7402	Intermediate Similarity	NPD6649	Approved
0.7402	Intermediate Similarity	NPD6650	Approved
0.7385	Intermediate Similarity	NPD7115	Discovery
0.7381	Intermediate Similarity	NPD4061	Clinical (unspecified phase)
0.7368	Intermediate Similarity	NPD5988	Approved
0.7323	Intermediate Similarity	NPD5955	Clinical (unspecified phase)
0.7302	Intermediate Similarity	NPD6881	Approved
0.7302	Intermediate Similarity	NPD6899	Approved
0.728	Intermediate Similarity	NPD6008	Approved
0.7222	Intermediate Similarity	NPD5701	Approved
0.7222	Intermediate Similarity	NPD5697	Approved
0.7209	Intermediate Similarity	NPD6053	Discontinued
0.7188	Intermediate Similarity	NPD7290	Approved
0.7188	Intermediate Similarity	NPD6883	Approved
0.7188	Intermediate Similarity	NPD7102	Approved
0.7165	Intermediate Similarity	NPD5345	Clinical (unspecified phase)
0.7132	Intermediate Similarity	NPD6847	Approved
0.7132	Intermediate Similarity	NPD8130	Phase 1
0.7132	Intermediate Similarity	NPD6869	Approved
0.7132	Intermediate Similarity	NPD6617	Approved
0.7109	Intermediate Similarity	NPD6013	Approved
0.7109	Intermediate Similarity	NPD6014	Approved
0.7109	Intermediate Similarity	NPD6012	Approved
0.7101	Intermediate Similarity	NPD6033	Approved
0.7087	Intermediate Similarity	NPD5954	Clinical (unspecified phase)
0.7059	Intermediate Similarity	NPD6067	Discontinued
0.7059	Intermediate Similarity	NPD7604	Phase 2
0.704	Intermediate Similarity	NPD7632	Discontinued
0.7037	Intermediate Similarity	NPD5983	Phase 2
0.7031	Intermediate Similarity	NPD6011	Approved
0.7	Intermediate Similarity	NPD8413	Clinical (unspecified phase)
0.7	Intermediate Similarity	NPD6401	Clinical (unspecified phase)
0.6992	Remote Similarity	NPD4755	Approved
0.6957	Remote Similarity	NPD6336	Discontinued
0.6923	Remote Similarity	NPD4634	Approved
0.6905	Remote Similarity	NPD5211	Phase 2
0.688	Remote Similarity	NPD4700	Approved
0.688	Remote Similarity	NPD5286	Approved
0.688	Remote Similarity	NPD5285	Approved
0.688	Remote Similarity	NPD4696	Approved
0.6855	Remote Similarity	NPD6083	Phase 2
0.6855	Remote Similarity	NPD7902	Approved
0.6855	Remote Similarity	NPD6084	Phase 2
0.6803	Remote Similarity	NPD8171	Discontinued
0.68	Remote Similarity	NPD4225	Approved
0.6797	Remote Similarity	NPD5141	Approved
0.6791	Remote Similarity	NPD6274	Approved
0.6786	Remote Similarity	NPD8074	Phase 3
0.6774	Remote Similarity	NPD4697	Phase 3
0.6772	Remote Similarity	NPD4633	Approved
0.6772	Remote Similarity	NPD5224	Approved
0.6772	Remote Similarity	NPD5226	Approved
0.6772	Remote Similarity	NPD5225	Approved
0.6765	Remote Similarity	NPD7100	Approved
0.6765	Remote Similarity	NPD7101	Approved
0.6748	Remote Similarity	NPD7748	Approved
0.6744	Remote Similarity	NPD4768	Approved
0.6744	Remote Similarity	NPD4767	Approved
0.6721	Remote Similarity	NPD8034	Phase 2
0.6721	Remote Similarity	NPD7515	Phase 2
0.6721	Remote Similarity	NPD8035	Phase 2
0.6719	Remote Similarity	NPD5175	Approved
0.6719	Remote Similarity	NPD5174	Approved
0.6694	Remote Similarity	NPD6356	Clinical (unspecified phase)
0.6694	Remote Similarity	NPD5328	Approved
0.6693	Remote Similarity	NPD5223	Approved
0.6692	Remote Similarity	NPD7899	Clinical (unspecified phase)
0.6691	Remote Similarity	NPD6335	Approved
0.6667	Remote Similarity	NPD4202	Approved
0.6667	Remote Similarity	NPD6399	Phase 3
0.6667	Remote Similarity	NPD6291	Clinical (unspecified phase)
0.6667	Remote Similarity	NPD6908	Approved
0.6667	Remote Similarity	NPD5696	Approved
0.6667	Remote Similarity	NPD6921	Approved
0.6667	Remote Similarity	NPD6371	Approved
0.6667	Remote Similarity	NPD6909	Approved
0.6641	Remote Similarity	NPD4730	Approved
0.6641	Remote Similarity	NPD4729	Approved
0.6639	Remote Similarity	NPD6698	Approved
0.6639	Remote Similarity	NPD46	Approved
0.6627	Remote Similarity	NPD7799	Discontinued
0.6618	Remote Similarity	NPD6317	Approved
0.6613	Remote Similarity	NPD7900	Approved
0.6613	Remote Similarity	NPD7901	Clinical (unspecified phase)
0.6612	Remote Similarity	NPD7513	Clinical (unspecified phase)
0.6589	Remote Similarity	NPD4754	Approved
0.6585	Remote Similarity	NPD6079	Approved
0.6569	Remote Similarity	NPD6313	Approved
0.6569	Remote Similarity	NPD6314	Approved
0.656	Remote Similarity	NPD5695	Phase 3
0.6541	Remote Similarity	NPD5250	Approved
0.6541	Remote Similarity	NPD5251	Approved
0.6541	Remote Similarity	NPD5248	Approved
0.6541	Remote Similarity	NPD5247	Approved
0.6541	Remote Similarity	NPD5249	Phase 3
0.6535	Remote Similarity	NPD8029	Clinical (unspecified phase)
0.6515	Remote Similarity	NPD5128	Approved
0.65	Remote Similarity	NPD7520	Clinical (unspecified phase)
0.6483	Remote Similarity	NPD7260	Phase 2
0.6479	Remote Similarity	NPD8451	Approved
0.6475	Remote Similarity	NPD6903	Approved
0.6452	Remote Similarity	NPD5693	Phase 1
0.6446	Remote Similarity	NPD5330	Approved
0.6446	Remote Similarity	NPD7334	Approved
0.6446	Remote Similarity	NPD6409	Approved
0.6446	Remote Similarity	NPD3618	Phase 1
0.6446	Remote Similarity	NPD6684	Approved
0.6446	Remote Similarity	NPD7146	Approved
0.6446	Remote Similarity	NPD7521	Approved
0.6434	Remote Similarity	NPD8448	Approved
0.6434	Remote Similarity	NPD5344	Discontinued
0.6423	Remote Similarity	NPD4753	Phase 2
0.6414	Remote Similarity	NPD8392	Approved
0.6414	Remote Similarity	NPD8390	Approved
0.6414	Remote Similarity	NPD5956	Approved
0.6414	Remote Similarity	NPD8391	Approved
0.6389	Remote Similarity	NPD8337	Approved
0.6389	Remote Similarity	NPD8336	Approved
0.6378	Remote Similarity	NPD5222	Approved
0.6378	Remote Similarity	NPD5221	Approved
0.6378	Remote Similarity	NPD5220	Clinical (unspecified phase)
0.637	Remote Similarity	NPD5215	Approved
0.637	Remote Similarity	NPD5217	Approved
0.637	Remote Similarity	NPD5216	Approved
0.6349	Remote Similarity	NPD6001	Approved
0.6338	Remote Similarity	NPD7642	Approved
0.6328	Remote Similarity	NPD5173	Approved
0.6327	Remote Similarity	NPD6845	Suspended
0.6327	Remote Similarity	NPD8338	Approved
0.6327	Remote Similarity	NPD8449	Approved
0.632	Remote Similarity	NPD5284	Approved
0.632	Remote Similarity	NPD5281	Approved
0.6304	Remote Similarity	NPD6868	Approved
0.6299	Remote Similarity	NPD5210	Approved
0.6299	Remote Similarity	NPD4629	Approved
0.6296	Remote Similarity	NPD5169	Approved
0.6296	Remote Similarity	NPD5134	Clinical (unspecified phase)
0.6296	Remote Similarity	NPD5135	Approved
0.6294	Remote Similarity	NPD8299	Approved
0.6294	Remote Similarity	NPD8340	Approved
0.6294	Remote Similarity	NPD8342	Approved
0.6294	Remote Similarity	NPD8341	Approved
0.629	Remote Similarity	NPD6051	Approved
0.629	Remote Similarity	NPD6673	Approved
0.629	Remote Similarity	NPD6904	Approved
0.629	Remote Similarity	NPD6080	Approved
0.6284	Remote Similarity	NPD8450	Suspended
0.6281	Remote Similarity	NPD3665	Phase 1
0.6281	Remote Similarity	NPD3133	Approved

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