NPASS Compound

Structure

Physi-Chem Properties

Molecular Weight:	488.28
Volume:	501.048
LogP:	3.392
LogD:	2.805
LogS:	-4.492
# Rotatable Bonds:	7
TPSA:	99.27
# H-Bond Aceptor:	7
# H-Bond Donor:	0
# Rings:	5
# Heavy Atoms:	7

MedChem Properties

QED Drug-Likeness Score:	0.423
Synthetic Accessibility Score:	5.858
Fsp3:	0.857
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Accepted
GSK Rule:	Rejected
BMS Rule:	0
Golden Triangle Rule:	Accepted
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-5.053
MDCK Permeability:	2.613738070067484e-05
Pgp-inhibitor:	0.997
Pgp-substrate:	0.011
Human Intestinal Absorption (HIA):	0.006
20% Bioavailability (F20%):	0.021
30% Bioavailability (F30%):	0.937

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.972
Plasma Protein Binding (PPB):	56.388145446777344%
Volume Distribution (VD):	0.687
Pgp-substrate:	49.603919982910156%

ADMET: Metabolism

CYP1A2-inhibitor:	0.018
CYP1A2-substrate:	0.886
CYP2C19-inhibitor:	0.039
CYP2C19-substrate:	0.785
CYP2C9-inhibitor:	0.031
CYP2C9-substrate:	0.019
CYP2D6-inhibitor:	0.013
CYP2D6-substrate:	0.16
CYP3A4-inhibitor:	0.813
CYP3A4-substrate:	0.671

ADMET: Excretion

Clearance (CL):	13.708
Half-life (T1/2):	0.372

ADMET: Toxicity

hERG Blockers:	0.084
Human Hepatotoxicity (H-HT):	0.465
Drug-inuced Liver Injury (DILI):	0.402
AMES Toxicity:	0.015
Rat Oral Acute Toxicity:	0.903
Maximum Recommended Daily Dose:	0.381
Skin Sensitization:	0.701
Carcinogencity:	0.744
Eye Corrosion:	0.148
Eye Irritation:	0.024
Respiratory Toxicity:	0.986

Download Data

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

Natural Product: NPC477495

Natural Product ID:	NPC477495
*Common Name:**	[(1S,3R,6S,7S,8S,9S,10S,11S,16S)-6-acetyl-8-acetyloxy-7,11-dimethyl-14-oxo-2-oxapentacyclo[8.8.0.01,3.03,7.011,16]octadecan-9-yl] 2-methylbutanoate
IUPAC Name:	[(1S,3R,6S,7S,8S,9S,10S,11S,16S)-6-acetyl-8-acetyloxy-7,11-dimethyl-14-oxo-2-oxapentacyclo[8.8.0.01,3.03,7.011,16]octadecan-9-yl] 2-methylbutanoate
Synonyms:
Standard InCHIKey:	NQDRVWQAEFRUEQ-ZFEXEXADSA-N
Standard InCHI:	InChI=1S/C28H40O7/c1-7-15(2)24(32)34-21-22-25(5)11-9-19(31)14-18(25)8-12-27(22)28(35-27)13-10-20(16(3)29)26(28,6)23(21)33-17(4)30/h15,18,20-23H,7-14H2,1-6H3/t15?,18-,20+,21-,22+,23+,25-,26-,27-,28+/m0/s1
SMILES:	CCC(C)C(=O)O[C@H]1[C@@H]2[C@]3(CCC(=O)C[C@@H]3CC[C@@]24[C@@]5(O4)CC[C@@H]([C@]5([C@@H]1OC(=O)C)C)C(=O)C)C
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	n.a.
PubChem CID:	118724164
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000258] Steroids and steroid derivatives [CHEMONTID:0001691] Steroid esters

*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
NPO23320	Marsdenia tenacissima	Species	Apocynaceae	Eukaryota	stems	Simao County, Yunnan Province, China	2005-MAR	PMID[25215856]
NPO23320	Marsdenia tenacissima	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO23320	Marsdenia tenacissima	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]

☑ 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
IC50	20
Others	4

Activity Type	# Activity
Cell Line	4
Others	20

Target ID	Target Type	Target Name	Activity Type	Activity Relation	Value	Unit	Reference
NPT2452	Cell Line	NCI-H292	IC50	=	840	nM	PMID[25215856]
NPT2452	Cell Line	NCI-H292	IC50	=	600	nM	PMID[25215856]
NPT2452	Cell Line	NCI-H292	IC50	=	140	nM	PMID[25215856]
NPT2452	Cell Line	NCI-H292	IC50	=	160	nM	PMID[25215856]
NPT2	Others	Unspecified	IC50	=	110	nM	PMID[25215856]
NPT2	Others	Unspecified	IC50	=	220	nM	PMID[25215856]
NPT2	Others	Unspecified	IC50	=	2100	nM	PMID[25215856]
NPT2	Others	Unspecified	IC50	=	850	nM	PMID[25215856]
NPT2	Others	Unspecified	IC50	=	11500	nM	PMID[25215856]
NPT2	Others	Unspecified	IC50	=	9400	nM	PMID[25215856]
NPT2	Others	Unspecified	IC50	=	12000	nM	PMID[25215856]
NPT2	Others	Unspecified	IC50	=	10200	nM	PMID[25215856]
NPT2	Others	Unspecified	Ratio IC50	=	19	n.a.	PMID[25215856]
NPT2	Others	Unspecified	Ratio IC50	=	4	n.a.	PMID[25215856]
NPT2	Others	Unspecified	Ratio IC50	=	1	n.a.	PMID[25215856]
NPT2	Others	Unspecified	Ratio IC50	=	1.1	n.a.	PMID[25215856]
NPT2	Others	Unspecified	IC50	=	5400	nM	PMID[25215856]
NPT2	Others	Unspecified	IC50	=	11100	nM	PMID[25215856]
NPT2	Others	Unspecified	IC50	=	3100	nM	PMID[25215856]
NPT2	Others	Unspecified	IC50	=	6500	nM	PMID[25215856]
NPT2	Others	Unspecified	IC50	=	11300	nM	PMID[25215856]
NPT2	Others	Unspecified	IC50	=	32200	nM	PMID[25215856]
NPT2	Others	Unspecified	IC50	=	7200	nM	PMID[25215856]
NPT2	Others	Unspecified	IC50	=	21800	nM	PMID[25215856]

☑ 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 NPC477495 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	526
0.1-0.2	4194
0.2-0.3	9153
0.3-0.4	13582
0.4-0.5	5657
0.5-0.6	5847
0.6-0.7	3033
0.7-0.8	661
0.8-0.85	42
0.85-0.9	1
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
0.8447	Intermediate Similarity	NPC477489
0.8404	Intermediate Similarity	NPC476189
0.837	Intermediate Similarity	NPC476379
0.8333	Intermediate Similarity	NPC116683
0.8333	Intermediate Similarity	NPC235109
0.8333	Intermediate Similarity	NPC163685
0.8316	Intermediate Similarity	NPC470423
0.8298	Intermediate Similarity	NPC52756
0.8298	Intermediate Similarity	NPC216137
0.8247	Intermediate Similarity	NPC471241
0.8247	Intermediate Similarity	NPC266417
0.8229	Intermediate Similarity	NPC17336
0.8229	Intermediate Similarity	NPC82633
0.8229	Intermediate Similarity	NPC470031
0.8211	Intermediate Similarity	NPC474379
0.82	Intermediate Similarity	NPC471253
0.82	Intermediate Similarity	NPC473406
0.8191	Intermediate Similarity	NPC77756
0.819	Intermediate Similarity	NPC97002
0.8172	Intermediate Similarity	NPC477614
0.8172	Intermediate Similarity	NPC226491
0.8152	Intermediate Similarity	NPC472272
0.8125	Intermediate Similarity	NPC470424
0.8119	Intermediate Similarity	NPC100078
0.81	Intermediate Similarity	NPC213528
0.81	Intermediate Similarity	NPC470172
0.81	Intermediate Similarity	NPC471254
0.81	Intermediate Similarity	NPC244969
0.8095	Intermediate Similarity	NPC477492
0.809	Intermediate Similarity	NPC125366
0.8046	Intermediate Similarity	NPC471046
0.8043	Intermediate Similarity	NPC266651
0.8041	Intermediate Similarity	NPC62407
0.8041	Intermediate Similarity	NPC287354
0.8039	Intermediate Similarity	NPC166079
0.8039	Intermediate Similarity	NPC306776
0.802	Intermediate Similarity	NPC34562
0.798	Intermediate Similarity	NPC253995
0.7959	Intermediate Similarity	NPC476728
0.7955	Intermediate Similarity	NPC143250
0.7941	Intermediate Similarity	NPC328737
0.7941	Intermediate Similarity	NPC327093
0.7935	Intermediate Similarity	NPC65133
0.7912	Intermediate Similarity	NPC477284
0.7895	Intermediate Similarity	NPC61688
0.7895	Intermediate Similarity	NPC56962
0.7895	Intermediate Similarity	NPC24705
0.7889	Intermediate Similarity	NPC134227
0.7872	Intermediate Similarity	NPC202937
0.7872	Intermediate Similarity	NPC263802
0.7872	Intermediate Similarity	NPC239938
0.7849	Intermediate Similarity	NPC473350
0.7835	Intermediate Similarity	NPC228700
0.7826	Intermediate Similarity	NPC259173
0.7822	Intermediate Similarity	NPC259654
0.7822	Intermediate Similarity	NPC121218
0.7822	Intermediate Similarity	NPC178853
0.7822	Intermediate Similarity	NPC298266
0.7822	Intermediate Similarity	NPC253886
0.7812	Intermediate Similarity	NPC470114
0.781	Intermediate Similarity	NPC227879
0.781	Intermediate Similarity	NPC208333
0.7802	Intermediate Similarity	NPC329490
0.7802	Intermediate Similarity	NPC328639
0.78	Intermediate Similarity	NPC476294
0.7789	Intermediate Similarity	NPC476435
0.7778	Intermediate Similarity	NPC477287
0.7778	Intermediate Similarity	NPC470115
0.7778	Intermediate Similarity	NPC476176
0.7778	Intermediate Similarity	NPC470116
0.7767	Intermediate Similarity	NPC301787
0.7767	Intermediate Similarity	NPC470167
0.7766	Intermediate Similarity	NPC475729
0.7766	Intermediate Similarity	NPC474215
0.7766	Intermediate Similarity	NPC80700
0.7766	Intermediate Similarity	NPC476727
0.7766	Intermediate Similarity	NPC302111
0.7766	Intermediate Similarity	NPC477441
0.7766	Intermediate Similarity	NPC476726
0.7766	Intermediate Similarity	NPC131365
0.7745	Intermediate Similarity	NPC170615
0.7742	Intermediate Similarity	NPC471044
0.7742	Intermediate Similarity	NPC50438
0.7742	Intermediate Similarity	NPC473336
0.7717	Intermediate Similarity	NPC317066
0.7717	Intermediate Similarity	NPC13494
0.7717	Intermediate Similarity	NPC60018
0.7717	Intermediate Similarity	NPC154043
0.7717	Intermediate Similarity	NPC202688
0.7717	Intermediate Similarity	NPC121121
0.7714	Intermediate Similarity	NPC316930
0.7714	Intermediate Similarity	NPC218123
0.7714	Intermediate Similarity	NPC112895
0.7714	Intermediate Similarity	NPC231278
0.7708	Intermediate Similarity	NPC472233
0.7708	Intermediate Similarity	NPC472234
0.7706	Intermediate Similarity	NPC475490
0.77	Intermediate Similarity	NPC472273
0.7699	Intermediate Similarity	NPC135038
0.7699	Intermediate Similarity	NPC267822
0.7699	Intermediate Similarity	NPC43252
0.7692	Intermediate Similarity	NPC472853
0.7692	Intermediate Similarity	NPC474714
0.7692	Intermediate Similarity	NPC222833
0.7692	Intermediate Similarity	NPC138908
0.7692	Intermediate Similarity	NPC200957
0.7684	Intermediate Similarity	NPC5943
0.767	Intermediate Similarity	NPC107385
0.7664	Intermediate Similarity	NPC94650
0.7653	Intermediate Similarity	NPC161035
0.7647	Intermediate Similarity	NPC252614
0.7642	Intermediate Similarity	NPC320475
0.7642	Intermediate Similarity	NPC321661
0.7634	Intermediate Similarity	NPC327451
0.7634	Intermediate Similarity	NPC227170
0.7632	Intermediate Similarity	NPC169818
0.7629	Intermediate Similarity	NPC472146
0.7629	Intermediate Similarity	NPC185529
0.7624	Intermediate Similarity	NPC38296
0.7624	Intermediate Similarity	NPC162459
0.7624	Intermediate Similarity	NPC38471
0.7624	Intermediate Similarity	NPC472144
0.7624	Intermediate Similarity	NPC28864
0.7624	Intermediate Similarity	NPC20479
0.7624	Intermediate Similarity	NPC98837
0.7619	Intermediate Similarity	NPC166993
0.7614	Intermediate Similarity	NPC55508
0.7611	Intermediate Similarity	NPC65858
0.7609	Intermediate Similarity	NPC469745
0.7604	Intermediate Similarity	NPC471221
0.76	Intermediate Similarity	NPC475785
0.76	Intermediate Similarity	NPC475765
0.76	Intermediate Similarity	NPC477264
0.7596	Intermediate Similarity	NPC88469
0.7596	Intermediate Similarity	NPC47281
0.7582	Intermediate Similarity	NPC320144
0.7582	Intermediate Similarity	NPC201276
0.7582	Intermediate Similarity	NPC80891
0.7579	Intermediate Similarity	NPC472745
0.7579	Intermediate Similarity	NPC477283
0.7579	Intermediate Similarity	NPC83242
0.7579	Intermediate Similarity	NPC215968
0.7579	Intermediate Similarity	NPC155531
0.7579	Intermediate Similarity	NPC474448
0.7556	Intermediate Similarity	NPC471151
0.7556	Intermediate Similarity	NPC474404
0.7553	Intermediate Similarity	NPC473299
0.7553	Intermediate Similarity	NPC291310
0.7553	Intermediate Similarity	NPC9060
0.7553	Intermediate Similarity	NPC477434
0.7553	Intermediate Similarity	NPC319909
0.7553	Intermediate Similarity	NPC181871
0.7551	Intermediate Similarity	NPC473066
0.7551	Intermediate Similarity	NPC474065
0.7549	Intermediate Similarity	NPC41843
0.7549	Intermediate Similarity	NPC293866
0.7547	Intermediate Similarity	NPC273155
0.7528	Intermediate Similarity	NPC72444
0.7527	Intermediate Similarity	NPC61107
0.7527	Intermediate Similarity	NPC289486
0.7527	Intermediate Similarity	NPC477936
0.7526	Intermediate Similarity	NPC471459
0.7526	Intermediate Similarity	NPC67653
0.7526	Intermediate Similarity	NPC477440
0.7526	Intermediate Similarity	NPC200580
0.7526	Intermediate Similarity	NPC477443
0.7525	Intermediate Similarity	NPC472145
0.7525	Intermediate Similarity	NPC190080
0.7525	Intermediate Similarity	NPC111187
0.7525	Intermediate Similarity	NPC469810
0.7524	Intermediate Similarity	NPC28791
0.7524	Intermediate Similarity	NPC470587
0.7524	Intermediate Similarity	NPC295366
0.7524	Intermediate Similarity	NPC37600
0.7524	Intermediate Similarity	NPC50535
0.75	Intermediate Similarity	NPC477851
0.75	Intermediate Similarity	NPC215570
0.75	Intermediate Similarity	NPC305808
0.75	Intermediate Similarity	NPC470920
0.75	Intermediate Similarity	NPC109510
0.75	Intermediate Similarity	NPC470609
0.75	Intermediate Similarity	NPC473062
0.75	Intermediate Similarity	NPC209298
0.75	Intermediate Similarity	NPC469824
0.75	Intermediate Similarity	NPC277074
0.75	Intermediate Similarity	NPC16449
0.75	Intermediate Similarity	NPC122811
0.75	Intermediate Similarity	NPC87927
0.7478	Intermediate Similarity	NPC469790
0.7476	Intermediate Similarity	NPC477172
0.7476	Intermediate Similarity	NPC295276
0.7476	Intermediate Similarity	NPC46848
0.7475	Intermediate Similarity	NPC122083
0.7475	Intermediate Similarity	NPC472231
0.7475	Intermediate Similarity	NPC182740
0.7475	Intermediate Similarity	NPC256104
0.7475	Intermediate Similarity	NPC472232
0.7475	Intermediate Similarity	NPC211845
0.7474	Intermediate Similarity	NPC474572
0.7474	Intermediate Similarity	NPC477445

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 NPC477495 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	520
0.1-0.2	4036
0.2-0.3	3081
0.3-0.4	894
0.4-0.5	287
0.5-0.6	193
0.6-0.7	126
0.7-0.8	13
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
0.8	Intermediate Similarity	NPD1700	Approved
0.7586	Intermediate Similarity	NPD5777	Approved
0.7524	Intermediate Similarity	NPD6008	Approved
0.7473	Intermediate Similarity	NPD6118	Approved
0.7473	Intermediate Similarity	NPD6114	Approved
0.7473	Intermediate Similarity	NPD6697	Approved
0.7473	Intermediate Similarity	NPD6115	Approved
0.7363	Intermediate Similarity	NPD6116	Phase 1
0.7264	Intermediate Similarity	NPD8170	Clinical (unspecified phase)
0.7253	Intermediate Similarity	NPD6117	Approved
0.7222	Intermediate Similarity	NPD5345	Clinical (unspecified phase)
0.7143	Intermediate Similarity	NPD3702	Approved
0.7143	Intermediate Similarity	NPD3703	Phase 2
0.713	Intermediate Similarity	NPD5954	Clinical (unspecified phase)
0.7033	Intermediate Similarity	NPD6113	Clinical (unspecified phase)
0.6937	Remote Similarity	NPD5955	Clinical (unspecified phase)
0.6881	Remote Similarity	NPD6402	Approved
0.6881	Remote Similarity	NPD5739	Approved
0.6881	Remote Similarity	NPD6675	Approved
0.6881	Remote Similarity	NPD7128	Approved
0.6863	Remote Similarity	NPD8035	Phase 2
0.6863	Remote Similarity	NPD8034	Phase 2
0.6847	Remote Similarity	NPD6373	Approved
0.6847	Remote Similarity	NPD4061	Clinical (unspecified phase)
0.6847	Remote Similarity	NPD6372	Approved
0.6814	Remote Similarity	NPD8297	Approved
0.6813	Remote Similarity	NPD4809	Clinical (unspecified phase)
0.6813	Remote Similarity	NPD4808	Clinical (unspecified phase)
0.6757	Remote Similarity	NPD7320	Approved
0.6757	Remote Similarity	NPD6881	Approved
0.6757	Remote Similarity	NPD6899	Approved
0.6754	Remote Similarity	NPD4632	Approved
0.6726	Remote Similarity	NPD6649	Approved
0.6726	Remote Similarity	NPD6650	Approved
0.6703	Remote Similarity	NPD4244	Approved
0.6703	Remote Similarity	NPD4245	Approved
0.6701	Remote Similarity	NPD1779	Approved
0.6701	Remote Similarity	NPD1780	Approved
0.6695	Remote Similarity	NPD6319	Approved
0.6667	Remote Similarity	NPD5697	Approved
0.6667	Remote Similarity	NPD7604	Phase 2
0.6667	Remote Similarity	NPD6356	Clinical (unspecified phase)
0.6667	Remote Similarity	NPD5701	Approved
0.6667	Remote Similarity	NPD5360	Phase 3
0.6667	Remote Similarity	NPD5361	Clinical (unspecified phase)
0.6637	Remote Similarity	NPD7102	Approved
0.6637	Remote Similarity	NPD7290	Approved
0.6637	Remote Similarity	NPD6883	Approved
0.663	Remote Similarity	NPD6081	Approved
0.6612	Remote Similarity	NPD7492	Approved
0.6593	Remote Similarity	NPD3700	Clinical (unspecified phase)
0.6593	Remote Similarity	NPD3699	Clinical (unspecified phase)
0.6593	Remote Similarity	NPD3698	Phase 2
0.6585	Remote Similarity	NPD7736	Approved
0.6581	Remote Similarity	NPD6009	Approved
0.6579	Remote Similarity	NPD8130	Phase 1
0.6579	Remote Similarity	NPD6847	Approved
0.6579	Remote Similarity	NPD6869	Approved
0.6579	Remote Similarity	NPD6617	Approved
0.6557	Remote Similarity	NPD7507	Approved
0.6557	Remote Similarity	NPD6616	Approved
0.6555	Remote Similarity	NPD6054	Approved
0.6555	Remote Similarity	NPD6059	Approved
0.6549	Remote Similarity	NPD6012	Approved
0.6549	Remote Similarity	NPD6013	Approved
0.6549	Remote Similarity	NPD6014	Approved
0.6532	Remote Similarity	NPD7319	Approved
0.6522	Remote Similarity	NPD6882	Approved
0.6504	Remote Similarity	NPD8293	Discontinued
0.6504	Remote Similarity	NPD7078	Approved
0.65	Remote Similarity	NPD5983	Phase 2
0.65	Remote Similarity	NPD6921	Approved
0.6476	Remote Similarity	NPD6399	Phase 3
0.6466	Remote Similarity	NPD8133	Approved
0.646	Remote Similarity	NPD6011	Approved
0.6446	Remote Similarity	NPD6370	Approved
0.6444	Remote Similarity	NPD4224	Phase 2
0.6436	Remote Similarity	NPD7520	Clinical (unspecified phase)
0.6435	Remote Similarity	NPD6401	Clinical (unspecified phase)
0.6429	Remote Similarity	NPD6928	Phase 2
0.6423	Remote Similarity	NPD6336	Discontinued
0.6413	Remote Similarity	NPD4267	Clinical (unspecified phase)
0.6408	Remote Similarity	NPD7513	Clinical (unspecified phase)
0.6404	Remote Similarity	NPD8132	Clinical (unspecified phase)
0.6389	Remote Similarity	NPD4755	Approved
0.6373	Remote Similarity	NPD7146	Approved
0.6373	Remote Similarity	NPD7521	Approved
0.6373	Remote Similarity	NPD5330	Approved
0.6373	Remote Similarity	NPD6684	Approved
0.6373	Remote Similarity	NPD7334	Approved
0.6373	Remote Similarity	NPD6409	Approved
0.6364	Remote Similarity	NPD6016	Approved
0.6364	Remote Similarity	NPD6015	Approved
0.6344	Remote Similarity	NPD4789	Approved
0.6333	Remote Similarity	NPD7516	Approved
0.633	Remote Similarity	NPD7638	Approved
0.6321	Remote Similarity	NPD8171	Discontinued
0.6311	Remote Similarity	NPD5988	Approved
0.6303	Remote Similarity	NPD7115	Discovery
0.6277	Remote Similarity	NPD4758	Discontinued
0.6273	Remote Similarity	NPD5285	Approved
0.6273	Remote Similarity	NPD5286	Approved
0.6273	Remote Similarity	NPD4700	Approved
0.6273	Remote Similarity	NPD7640	Approved
0.6273	Remote Similarity	NPD4696	Approved
0.6273	Remote Similarity	NPD7639	Approved
0.6262	Remote Similarity	NPD7901	Clinical (unspecified phase)
0.6262	Remote Similarity	NPD6001	Approved
0.6262	Remote Similarity	NPD7900	Approved
0.625	Remote Similarity	NPD7327	Approved
0.625	Remote Similarity	NPD7328	Approved
0.625	Remote Similarity	NPD6903	Approved
0.6239	Remote Similarity	NPD6084	Phase 2
0.6239	Remote Similarity	NPD6083	Phase 2
0.6228	Remote Similarity	NPD6412	Phase 2
0.6224	Remote Similarity	NPD5364	Discontinued
0.6218	Remote Similarity	NPD6940	Discontinued
0.6218	Remote Similarity	NPD6274	Approved
0.6214	Remote Similarity	NPD6098	Approved
0.6207	Remote Similarity	NPD4634	Approved
0.6198	Remote Similarity	NPD7101	Approved
0.6198	Remote Similarity	NPD7100	Approved
0.619	Remote Similarity	NPD6080	Approved
0.619	Remote Similarity	NPD6904	Approved
0.619	Remote Similarity	NPD6673	Approved
0.6182	Remote Similarity	NPD5696	Approved
0.6167	Remote Similarity	NPD8295	Clinical (unspecified phase)
0.6161	Remote Similarity	NPD5211	Phase 2
0.6161	Remote Similarity	NPD5226	Approved
0.6161	Remote Similarity	NPD4633	Approved
0.6161	Remote Similarity	NPD5225	Approved
0.6161	Remote Similarity	NPD7632	Discontinued
0.6161	Remote Similarity	NPD5224	Approved
0.6154	Remote Similarity	NPD3171	Clinical (unspecified phase)
0.6126	Remote Similarity	NPD8418	Phase 2
0.6116	Remote Similarity	NPD6335	Approved
0.6106	Remote Similarity	NPD5174	Approved
0.6106	Remote Similarity	NPD5175	Approved
0.6098	Remote Similarity	NPD6909	Approved
0.6098	Remote Similarity	NPD6908	Approved
0.6095	Remote Similarity	NPD5737	Approved
0.6095	Remote Similarity	NPD6672	Approved
0.6091	Remote Similarity	NPD7902	Approved
0.6078	Remote Similarity	NPD3669	Approved
0.6078	Remote Similarity	NPD4788	Approved
0.6078	Remote Similarity	NPD3670	Clinical (unspecified phase)
0.6071	Remote Similarity	NPD5223	Approved
0.6063	Remote Similarity	NPD6033	Approved
0.6061	Remote Similarity	NPD3671	Phase 1
0.6061	Remote Similarity	NPD4802	Phase 2
0.6061	Remote Similarity	NPD4238	Approved
0.6055	Remote Similarity	NPD5695	Phase 3
0.6053	Remote Similarity	NPD5141	Approved
0.6038	Remote Similarity	NPD5328	Approved
0.6033	Remote Similarity	NPD6317	Approved
0.6019	Remote Similarity	NPD4202	Approved
0.6	Remote Similarity	NPD4787	Phase 1
0.6	Remote Similarity	NPD4767	Approved
0.6	Remote Similarity	NPD4768	Approved
0.6	Remote Similarity	NPD8328	Phase 3
0.5984	Remote Similarity	NPD6314	Approved
0.5984	Remote Similarity	NPD6313	Approved
0.5968	Remote Similarity	NPD8296	Approved
0.5968	Remote Similarity	NPD6291	Clinical (unspecified phase)
0.5968	Remote Similarity	NPD8335	Approved
0.5968	Remote Similarity	NPD8378	Approved
0.5968	Remote Similarity	NPD8380	Approved
0.5968	Remote Similarity	NPD8379	Approved
0.5965	Remote Similarity	NPD4754	Approved
0.5963	Remote Similarity	NPD7748	Approved
0.5943	Remote Similarity	NPD5208	Approved
0.5926	Remote Similarity	NPD6079	Approved
0.5926	Remote Similarity	NPD5693	Phase 1
0.5926	Remote Similarity	NPD6050	Approved
0.5913	Remote Similarity	NPD4057	Clinical (unspecified phase)
0.5913	Remote Similarity	NPD4056	Clinical (unspecified phase)
0.5897	Remote Similarity	NPD4730	Approved
0.5897	Remote Similarity	NPD5128	Approved
0.5897	Remote Similarity	NPD4729	Approved
0.5887	Remote Similarity	NPD8294	Approved
0.5887	Remote Similarity	NPD8377	Approved
0.5856	Remote Similarity	NPD4697	Phase 3
0.5849	Remote Similarity	NPD3573	Approved
0.584	Remote Similarity	NPD8033	Approved
0.5833	Remote Similarity	NPD7532	Clinical (unspecified phase)
0.5833	Remote Similarity	NPD5207	Approved
0.5833	Remote Similarity	NPD6053	Discontinued
0.5833	Remote Similarity	NPD5692	Phase 3
0.5798	Remote Similarity	NPD5247	Approved
0.5798	Remote Similarity	NPD5248	Approved
0.5798	Remote Similarity	NPD5249	Phase 3
0.5798	Remote Similarity	NPD5250	Approved
0.5798	Remote Similarity	NPD5251	Approved
0.5789	Remote Similarity	NPD229	Approved
0.578	Remote Similarity	NPD5694	Approved
0.578	Remote Similarity	NPD5284	Approved
0.578	Remote Similarity	NPD7515	Phase 2
0.578	Remote Similarity	NPD5281	Approved
0.5766	Remote Similarity	NPD7991	Discontinued
0.5755	Remote Similarity	NPD3618	Phase 1

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