NPASS Compound

Structure

NPC47761 OpenBabel07101718302D 30 33 0 0 1 0 0 0 0 0999 V2000 4.8363 2.9680 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5773 6.5914 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8341 5.9223 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1913 2.4135 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4980 4.4543 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1890 3.5032 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8660 -1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7321 -1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1369 1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5491 0.1910 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7321 0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8660 1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4762 4.6622 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8660 0.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7321 2.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8660 -1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8581 2.7601 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.0000 -1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7321 -1.0000 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 1.7321 -0.0000 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 3.5491 1.8090 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 2.5981 0.5000 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 0.8660 0.5000 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 4.7852 5.6132 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0000 -0.0000 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 2.5981 1.5000 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.5981 -1.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 6.0724 6.7722 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 5.7633 5.8212 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2 25 1 0 0 0 0 3 25 1 0 0 0 0 6 7 1 0 0 0 0 6 14 2 0 0 0 0 7 18 1 0 0 0 0 8 9 1 0 0 0 0 8 19 2 0 0 0 0 10 11 1 0 0 0 0 10 22 1 0 0 0 0 11 23 1 0 0 0 0 12 15 1 0 0 0 0 12 20 1 0 0 0 0 13 16 1 0 0 0 0 13 24 1 0 0 0 0 14 25 1 0 0 0 0 15 26 1 0 0 0 0 16 27 1 0 0 0 0 17 19 1 0 0 0 0 17 20 1 0 0 0 0 18 1 1 1 0 0 0 18 22 1 0 0 0 0 19 26 1 0 0 0 0 20 28 1 1 0 0 0 21 9 1 6 0 0 0 21 23 1 0 0 0 0 21 24 1 0 0 0 0 22 27 1 1 0 0 0 23 27 1 1 0 0 0 24 26 1 1 0 0 0 25 30 1 0 0 0 0 26 4 1 1 0 0 0 27 5 1 1 0 0 0 29 30 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	416.33
Volume:	462.42
LogP:	5.881
LogD:	5.303
LogS:	-5.274
# Rotatable Bonds:	5
TPSA:	49.69
# H-Bond Aceptor:	3
# H-Bond Donor:	2
# Rings:	4
# Heavy Atoms:	3

MedChem Properties

QED Drug-Likeness Score:	0.295
Synthetic Accessibility Score:	4.7
Fsp3:	0.852
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected
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:	-4.589
MDCK Permeability:	2.06E-05
Pgp-inhibitor:	0.779
Pgp-substrate:	0.473
Human Intestinal Absorption (HIA):	0.008
20% Bioavailability (F20%):	0.955
30% Bioavailability (F30%):	0.037

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.216
Plasma Protein Binding (PPB):	97.60%
Volume Distribution (VD):	1.338
Pgp-substrate:	2.71%

ADMET: Metabolism

CYP1A2-inhibitor:	0.117
CYP1A2-substrate:	0.456
CYP2C19-inhibitor:	0.142
CYP2C19-substrate:	0.875
CYP2C9-inhibitor:	0.333
CYP2C9-substrate:	0.613
CYP2D6-inhibitor:	0.206
CYP2D6-substrate:	0.894
CYP3A4-inhibitor:	0.666
CYP3A4-substrate:	0.249

ADMET: Excretion

Clearance (CL):	3.672
Half-life (T1/2):	0.194

ADMET: Toxicity

hERG Blockers:	0.211
Human Hepatotoxicity (H-HT):	0.463
Drug-inuced Liver Injury (DILI):	0.255
AMES Toxicity:	0.036
Rat Oral Acute Toxicity:	0.008
Maximum Recommended Daily Dose:	0.92
Skin Sensitization:	0.95
Carcinogencity:	0.719
Eye Corrosion:	0.733
Eye Irritation:	0.77
Respiratory Toxicity:	0.978

Download Data

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

Natural Product: NPC47761

Natural Product ID:	NPC47761
*Common Name:**	25-Hydroperoxycholesta-5,23(E)-Dien-3Beta-Ol
IUPAC Name:	(3S,8S,9S,10R,13R,14S,17R)-17-[(E,2R)-6-hydroperoxy-6-methylhept-4-en-2-yl]-10,13-dimethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-ol
Synonyms:
Standard InCHIKey:	SISZKTSVHKUZKL-HUYSPLOCSA-N
Standard InCHI:	InChI=1S/C27H44O3/c1-18(7-6-14-25(2,3)30-29)22-10-11-23-21-9-8-19-17-20(28)12-15-26(19,4)24(21)13-16-27(22,23)5/h6,8,14,18,20-24,28-29H,7,9-13,15-17H2,1-5H3/b14-6+/t18-,20+,21+,22-,23+,24+,26+,27-/m1/s1
SMILES:	C[C@H](C/C=C/C(C)(C)OO)[C@H]1CC[C@H]2[C@@H]3CC=C4C[C@H](CC[C@]4(C)[C@H]3CC[C@]12C)O
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL458051
PubChem CID:	10764408
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000258] Steroids and steroid derivatives [CHEMONTID:0003566] Cholestane steroids [CHEMONTID:0001469] Cholesterols 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
NPO33302	galaxaura marginata	Species	Galaxauraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[8984148]
NPO33302	galaxaura marginata	Species	Galaxauraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[9322362]

☑ 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

Activity Type	# Activity
Cell Line	8

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT91	Cell Line	KB	Homo sapiens	ED50	=	1.41	ug ml-1	PMID[520314]
NPT81	Cell Line	A549	Homo sapiens	ED50	=	1.68	ug ml-1	PMID[520314]
NPT139	Cell Line	HT-29	Homo sapiens	ED50	=	1.27	ug ml-1	PMID[520314]
NPT168	Cell Line	P388	Mus musculus	ED50	=	0.22	ug ml-1	PMID[520314]
NPT168	Cell Line	P388	Mus musculus	ED50	=	0.22	ug ml-1	PMID[520315]
NPT91	Cell Line	KB	Homo sapiens	ED50	=	1.41	ug ml-1	PMID[520315]
NPT81	Cell Line	A549	Homo sapiens	ED50	=	1.68	ug ml-1	PMID[520315]
NPT139	Cell Line	HT-29	Homo sapiens	ED50	=	1.27	ug ml-1	PMID[520315]

☑ 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 NPC47761 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	152
0.1-0.2	1270
0.2-0.3	5743
0.3-0.4	15791
0.4-0.5	7957
0.5-0.6	6003
0.6-0.7	4301
0.7-0.8	1134
0.8-0.85	201
0.85-0.9	73
0.9-0.95	63
0.95-1	9

Similarity Score	Similarity Level	Natural Product ID
0.9737	High Similarity	NPC264245
0.961	High Similarity	NPC49964
0.9605	High Similarity	NPC209944
0.9605	High Similarity	NPC241290
0.9605	High Similarity	NPC164840
0.9605	High Similarity	NPC234193
0.96	High Similarity	NPC473943
0.9474	High Similarity	NPC81306
0.9474	High Similarity	NPC109546
0.9474	High Similarity	NPC84694
0.9474	High Similarity	NPC47982
0.9474	High Similarity	NPC143182
0.9474	High Similarity	NPC28862
0.9467	High Similarity	NPC155986
0.9467	High Similarity	NPC318495
0.9467	High Similarity	NPC198968
0.9367	High Similarity	NPC205845
0.9359	High Similarity	NPC50964
0.9342	High Similarity	NPC474216
0.9333	High Similarity	NPC107059
0.9333	High Similarity	NPC113733
0.9333	High Similarity	NPC321381
0.9333	High Similarity	NPC321016
0.925	High Similarity	NPC157257
0.925	High Similarity	NPC274448
0.925	High Similarity	NPC318390
0.9241	High Similarity	NPC475789
0.9241	High Similarity	NPC474634
0.9231	High Similarity	NPC7505
0.9231	High Similarity	NPC474752
0.9231	High Similarity	NPC474731
0.9231	High Similarity	NPC209620
0.9231	High Similarity	NPC474683
0.9231	High Similarity	NPC82986
0.9231	High Similarity	NPC23852
0.9231	High Similarity	NPC474759
0.9221	High Similarity	NPC328714
0.9221	High Similarity	NPC30986
0.9221	High Similarity	NPC209430
0.92	High Similarity	NPC134847
0.92	High Similarity	NPC288035
0.92	High Similarity	NPC162742
0.92	High Similarity	NPC285893
0.92	High Similarity	NPC28657
0.92	High Similarity	NPC136188
0.92	High Similarity	NPC304309
0.92	High Similarity	NPC22105
0.92	High Similarity	NPC230301
0.9136	High Similarity	NPC261266
0.9125	High Similarity	NPC238485
0.9125	High Similarity	NPC470077
0.9114	High Similarity	NPC101462
0.9114	High Similarity	NPC296701
0.9114	High Similarity	NPC87489
0.9114	High Similarity	NPC218616
0.9114	High Similarity	NPC189972
0.9091	High Similarity	NPC477514
0.9091	High Similarity	NPC477522
0.9091	High Similarity	NPC18603
0.9091	High Similarity	NPC307965
0.9091	High Similarity	NPC87604
0.9091	High Similarity	NPC76931
0.9079	High Similarity	NPC134330
0.9079	High Similarity	NPC247325
0.9079	High Similarity	NPC129165
0.9079	High Similarity	NPC300324
0.9079	High Similarity	NPC244488
0.9079	High Similarity	NPC240604
0.9024	High Similarity	NPC149224
0.9	High Similarity	NPC134481
0.9	High Similarity	NPC317458
0.8961	High Similarity	NPC34019
0.8947	High Similarity	NPC257347
0.8947	High Similarity	NPC141071
0.8947	High Similarity	NPC471723
0.8933	High Similarity	NPC471799
0.8902	High Similarity	NPC293287
0.8902	High Similarity	NPC6391
0.8902	High Similarity	NPC152808
0.8889	High Similarity	NPC185568
0.8889	High Similarity	NPC474047
0.8889	High Similarity	NPC231310
0.8875	High Similarity	NPC470049
0.8861	High Similarity	NPC26117
0.8846	High Similarity	NPC83351
0.8846	High Similarity	NPC275910
0.8846	High Similarity	NPC167891
0.8846	High Similarity	NPC285761
0.8831	High Similarity	NPC470362
0.8831	High Similarity	NPC189883
0.8831	High Similarity	NPC96319
0.8816	High Similarity	NPC471797
0.878	High Similarity	NPC470360
0.878	High Similarity	NPC266511
0.8765	High Similarity	NPC470558
0.8765	High Similarity	NPC82623
0.8765	High Similarity	NPC470384
0.875	High Similarity	NPC474531
0.875	High Similarity	NPC470383
0.8734	High Similarity	NPC1319
0.8734	High Similarity	NPC273410
0.8734	High Similarity	NPC80530
0.8718	High Similarity	NPC91594
0.8718	High Similarity	NPC214570
0.8706	High Similarity	NPC329596
0.8706	High Similarity	NPC204188
0.8706	High Similarity	NPC295668
0.8706	High Similarity	NPC192437
0.8706	High Similarity	NPC270511
0.8706	High Similarity	NPC80561
0.8706	High Similarity	NPC245410
0.8706	High Similarity	NPC14380
0.8706	High Similarity	NPC3345
0.8706	High Similarity	NPC291484
0.8706	High Similarity	NPC470390
0.8706	High Similarity	NPC11216
0.869	High Similarity	NPC474668
0.869	High Similarity	NPC133588
0.8684	High Similarity	NPC474140
0.8675	High Similarity	NPC299068
0.8667	High Similarity	NPC475728
0.8659	High Similarity	NPC33913
0.8642	High Similarity	NPC202389
0.8642	High Similarity	NPC470614
0.8642	High Similarity	NPC5985
0.8642	High Similarity	NPC1272
0.8642	High Similarity	NPC30166
0.8625	High Similarity	NPC236237
0.8625	High Similarity	NPC236112
0.8625	High Similarity	NPC13554
0.8625	High Similarity	NPC322313
0.8625	High Similarity	NPC102253
0.8608	High Similarity	NPC167037
0.8608	High Similarity	NPC138621
0.8608	High Similarity	NPC244385
0.8608	High Similarity	NPC6978
0.8605	High Similarity	NPC41554
0.8605	High Similarity	NPC97404
0.859	High Similarity	NPC237460
0.859	High Similarity	NPC73875
0.859	High Similarity	NPC265588
0.859	High Similarity	NPC46160
0.859	High Similarity	NPC202642
0.8588	High Similarity	NPC470361
0.8588	High Similarity	NPC101886
0.8571	High Similarity	NPC469593
0.8571	High Similarity	NPC469534
0.8571	High Similarity	NPC469533
0.8571	High Similarity	NPC477138
0.8571	High Similarity	NPC243342
0.8571	High Similarity	NPC329090
0.8571	High Similarity	NPC27395
0.8554	High Similarity	NPC474189
0.8554	High Similarity	NPC474349
0.8553	High Similarity	NPC242001
0.8519	High Similarity	NPC476646
0.8488	Intermediate Similarity	NPC320026
0.8481	Intermediate Similarity	NPC470758
0.8481	Intermediate Similarity	NPC471798
0.8481	Intermediate Similarity	NPC470711
0.8471	Intermediate Similarity	NPC4574
0.8471	Intermediate Similarity	NPC212596
0.8462	Intermediate Similarity	NPC291503
0.8462	Intermediate Similarity	NPC322353
0.8462	Intermediate Similarity	NPC471468
0.8462	Intermediate Similarity	NPC319090
0.8462	Intermediate Similarity	NPC118508
0.8462	Intermediate Similarity	NPC328104
0.8462	Intermediate Similarity	NPC121744
0.8452	Intermediate Similarity	NPC94462
0.8442	Intermediate Similarity	NPC182717
0.8434	Intermediate Similarity	NPC59453
0.8434	Intermediate Similarity	NPC221758
0.8434	Intermediate Similarity	NPC124172
0.8434	Intermediate Similarity	NPC209802
0.8434	Intermediate Similarity	NPC472265
0.8434	Intermediate Similarity	NPC474493
0.8421	Intermediate Similarity	NPC145498
0.8421	Intermediate Similarity	NPC34834
0.8415	Intermediate Similarity	NPC248886
0.8415	Intermediate Similarity	NPC201852
0.8409	Intermediate Similarity	NPC127718
0.8409	Intermediate Similarity	NPC292793
0.8409	Intermediate Similarity	NPC65402
0.8409	Intermediate Similarity	NPC8993
0.84	Intermediate Similarity	NPC160209
0.84	Intermediate Similarity	NPC208999
0.8395	Intermediate Similarity	NPC96362
0.8391	Intermediate Similarity	NPC475806
0.8375	Intermediate Similarity	NPC11908
0.8375	Intermediate Similarity	NPC476314
0.8375	Intermediate Similarity	NPC85346
0.8375	Intermediate Similarity	NPC65897
0.8375	Intermediate Similarity	NPC186191
0.8375	Intermediate Similarity	NPC302041
0.8375	Intermediate Similarity	NPC205455
0.8372	Intermediate Similarity	NPC2983
0.8372	Intermediate Similarity	NPC477606
0.8372	Intermediate Similarity	NPC146554
0.8372	Intermediate Similarity	NPC138974

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 NPC47761 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	152
0.1-0.2	1419
0.2-0.3	4262
0.3-0.4	2297
0.4-0.5	566
0.5-0.6	177
0.6-0.7	183
0.7-0.8	68
0.8-0.85	18
0.85-0.9	6
0.9-0.95	2
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.92	High Similarity	NPD6942	Approved
0.92	High Similarity	NPD7339	Approved
0.8831	High Similarity	NPD3701	Clinical (unspecified phase)
0.8625	High Similarity	NPD7525	Registered
0.8571	High Similarity	NPD6924	Approved
0.8571	High Similarity	NPD4784	Approved
0.8571	High Similarity	NPD4785	Approved
0.8571	High Similarity	NPD6926	Approved
0.8571	High Similarity	NPD4751	Clinical (unspecified phase)
0.8434	Intermediate Similarity	NPD4786	Approved
0.8354	Intermediate Similarity	NPD6933	Approved
0.8312	Intermediate Similarity	NPD7151	Approved
0.8312	Intermediate Similarity	NPD7150	Approved
0.8312	Intermediate Similarity	NPD7152	Approved
0.8312	Intermediate Similarity	NPD4243	Approved
0.8193	Intermediate Similarity	NPD3667	Approved
0.8182	Intermediate Similarity	NPD7143	Approved
0.8182	Intermediate Similarity	NPD7144	Approved
0.8171	Intermediate Similarity	NPD6931	Approved
0.8171	Intermediate Similarity	NPD7514	Phase 3
0.8171	Intermediate Similarity	NPD6930	Phase 2
0.8148	Intermediate Similarity	NPD7322	Clinical (unspecified phase)
0.8052	Intermediate Similarity	NPD6923	Approved
0.8052	Intermediate Similarity	NPD6922	Approved
0.8049	Intermediate Similarity	NPD6929	Approved
0.8025	Intermediate Similarity	NPD6932	Approved
0.7952	Intermediate Similarity	NPD4748	Discontinued
0.7952	Intermediate Similarity	NPD7332	Phase 2
0.7927	Intermediate Similarity	NPD7145	Approved
0.7882	Intermediate Similarity	NPD6695	Phase 3
0.7857	Intermediate Similarity	NPD6902	Approved
0.7831	Intermediate Similarity	NPD7645	Phase 2
0.7831	Intermediate Similarity	NPD4195	Approved
0.7805	Intermediate Similarity	NPD5776	Phase 2
0.7805	Intermediate Similarity	NPD6925	Approved
0.7791	Intermediate Similarity	NPD7338	Clinical (unspecified phase)
0.7778	Intermediate Similarity	NPD6079	Approved
0.7778	Intermediate Similarity	NPD4190	Phase 3
0.7778	Intermediate Similarity	NPD8264	Approved
0.7778	Intermediate Similarity	NPD5275	Approved
0.7753	Intermediate Similarity	NPD5328	Approved
0.7738	Intermediate Similarity	NPD7509	Discontinued
0.7701	Intermediate Similarity	NPD6893	Approved
0.7619	Intermediate Similarity	NPD6683	Phase 2
0.7614	Intermediate Similarity	NPD3618	Phase 1
0.7586	Intermediate Similarity	NPD3665	Phase 1
0.7586	Intermediate Similarity	NPD3666	Approved
0.7586	Intermediate Similarity	NPD3133	Approved
0.7528	Intermediate Similarity	NPD7750	Discontinued
0.7528	Intermediate Similarity	NPD7524	Approved
0.75	Intermediate Similarity	NPD4202	Approved
0.75	Intermediate Similarity	NPD6399	Phase 3
0.7442	Intermediate Similarity	NPD6898	Phase 1
0.7386	Intermediate Similarity	NPD3668	Phase 3
0.7363	Intermediate Similarity	NPD4753	Phase 2
0.7363	Intermediate Similarity	NPD6051	Approved
0.7356	Intermediate Similarity	NPD4223	Phase 3
0.7356	Intermediate Similarity	NPD4221	Approved
0.7303	Intermediate Similarity	NPD5329	Approved
0.7263	Intermediate Similarity	NPD5220	Clinical (unspecified phase)
0.7263	Intermediate Similarity	NPD5222	Approved
0.7263	Intermediate Similarity	NPD5221	Approved
0.7245	Intermediate Similarity	NPD5211	Phase 2
0.7222	Intermediate Similarity	NPD5279	Phase 3
0.7216	Intermediate Similarity	NPD5286	Approved
0.7216	Intermediate Similarity	NPD5285	Approved
0.7216	Intermediate Similarity	NPD4696	Approved
0.7204	Intermediate Similarity	NPD7087	Discontinued
0.7191	Intermediate Similarity	NPD4197	Approved
0.7188	Intermediate Similarity	NPD4755	Approved
0.7188	Intermediate Similarity	NPD5173	Approved
0.7158	Intermediate Similarity	NPD5210	Approved
0.7158	Intermediate Similarity	NPD4629	Approved
0.7143	Intermediate Similarity	NPD5223	Approved
0.7113	Intermediate Similarity	NPD7638	Approved
0.7111	Intermediate Similarity	NPD7520	Clinical (unspecified phase)
0.71	Intermediate Similarity	NPD5141	Approved
0.7083	Intermediate Similarity	NPD4697	Phase 3
0.7079	Intermediate Similarity	NPD4788	Approved
0.7071	Intermediate Similarity	NPD4633	Approved
0.7071	Intermediate Similarity	NPD5225	Approved
0.7071	Intermediate Similarity	NPD5226	Approved
0.7071	Intermediate Similarity	NPD5224	Approved
0.7041	Intermediate Similarity	NPD7639	Approved
0.7041	Intermediate Similarity	NPD4700	Approved
0.7041	Intermediate Similarity	NPD7640	Approved
0.7033	Intermediate Similarity	NPD4693	Phase 3
0.7033	Intermediate Similarity	NPD4689	Approved
0.7033	Intermediate Similarity	NPD4623	Approved
0.7033	Intermediate Similarity	NPD4138	Approved
0.7033	Intermediate Similarity	NPD4519	Discontinued
0.7033	Intermediate Similarity	NPD5690	Phase 2
0.7033	Intermediate Similarity	NPD4690	Approved
0.7033	Intermediate Similarity	NPD4688	Approved
0.7033	Intermediate Similarity	NPD5205	Approved
0.7021	Intermediate Similarity	NPD7637	Suspended
0.701	Intermediate Similarity	NPD6083	Phase 2
0.701	Intermediate Similarity	NPD6084	Phase 2
0.7	Intermediate Similarity	NPD5174	Approved
0.7	Intermediate Similarity	NPD5175	Approved
0.6951	Remote Similarity	NPD4267	Clinical (unspecified phase)
0.6939	Remote Similarity	NPD5290	Discontinued
0.6923	Remote Similarity	NPD368	Approved
0.6893	Remote Similarity	NPD6881	Approved
0.6893	Remote Similarity	NPD6899	Approved
0.6882	Remote Similarity	NPD4723	Approved
0.6882	Remote Similarity	NPD4722	Approved
0.6867	Remote Similarity	NPD4787	Phase 1
0.6863	Remote Similarity	NPD6402	Approved
0.6863	Remote Similarity	NPD7128	Approved
0.6863	Remote Similarity	NPD5739	Approved
0.6863	Remote Similarity	NPD6675	Approved
0.6852	Remote Similarity	NPD7115	Discovery
0.6848	Remote Similarity	NPD5330	Approved
0.6848	Remote Similarity	NPD7521	Approved
0.6848	Remote Similarity	NPD5280	Approved
0.6848	Remote Similarity	NPD4694	Approved
0.6848	Remote Similarity	NPD6684	Approved
0.6848	Remote Similarity	NPD7146	Approved
0.6848	Remote Similarity	NPD7334	Approved
0.6848	Remote Similarity	NPD6409	Approved
0.6842	Remote Similarity	NPD7515	Phase 2
0.6832	Remote Similarity	NPD4754	Approved
0.68	Remote Similarity	NPD4159	Approved
0.6796	Remote Similarity	NPD5697	Approved
0.6762	Remote Similarity	NPD7290	Approved
0.6762	Remote Similarity	NPD7102	Approved
0.6762	Remote Similarity	NPD6883	Approved
0.6737	Remote Similarity	NPD7136	Phase 2
0.6731	Remote Similarity	NPD7320	Approved
0.6731	Remote Similarity	NPD4730	Approved
0.6731	Remote Similarity	NPD6011	Approved
0.6731	Remote Similarity	NPD4729	Approved
0.6705	Remote Similarity	NPD3617	Approved
0.6705	Remote Similarity	NPD5784	Clinical (unspecified phase)
0.6702	Remote Similarity	NPD7513	Clinical (unspecified phase)
0.6702	Remote Similarity	NPD5737	Approved
0.6702	Remote Similarity	NPD6903	Approved
0.6702	Remote Similarity	NPD6672	Approved
0.6699	Remote Similarity	NPD4767	Approved
0.6699	Remote Similarity	NPD4768	Approved
0.6698	Remote Similarity	NPD6847	Approved
0.6698	Remote Similarity	NPD8130	Phase 1
0.6698	Remote Similarity	NPD6650	Approved
0.6698	Remote Similarity	NPD6617	Approved
0.6698	Remote Similarity	NPD6869	Approved
0.6698	Remote Similarity	NPD6649	Approved
0.6667	Remote Similarity	NPD4139	Approved
0.6667	Remote Similarity	NPD6014	Approved
0.6667	Remote Similarity	NPD6012	Approved
0.6667	Remote Similarity	NPD6372	Approved
0.6667	Remote Similarity	NPD5284	Approved
0.6667	Remote Similarity	NPD6013	Approved
0.6667	Remote Similarity	NPD6373	Approved
0.6667	Remote Similarity	NPD4692	Approved
0.6667	Remote Similarity	NPD3574	Clinical (unspecified phase)
0.6667	Remote Similarity	NPD6098	Approved
0.6667	Remote Similarity	NPD5281	Approved
0.6636	Remote Similarity	NPD6882	Approved
0.6636	Remote Similarity	NPD8297	Approved
0.6635	Remote Similarity	NPD5701	Approved
0.6633	Remote Similarity	NPD5695	Phase 3
0.6604	Remote Similarity	NPD5134	Clinical (unspecified phase)
0.6604	Remote Similarity	NPD5250	Approved
0.6604	Remote Similarity	NPD5249	Phase 3
0.6604	Remote Similarity	NPD5247	Approved
0.6604	Remote Similarity	NPD5251	Approved
0.6604	Remote Similarity	NPD5248	Approved
0.6604	Remote Similarity	NPD5135	Approved
0.6604	Remote Similarity	NPD4634	Approved
0.6604	Remote Similarity	NPD5169	Approved
0.66	Remote Similarity	NPD5696	Approved
0.6588	Remote Similarity	NPD4809	Clinical (unspecified phase)
0.6588	Remote Similarity	NPD4808	Clinical (unspecified phase)
0.6579	Remote Similarity	NPD342	Phase 1
0.6571	Remote Similarity	NPD5168	Approved
0.6571	Remote Similarity	NPD5128	Approved
0.6556	Remote Similarity	NPD4821	Approved
0.6556	Remote Similarity	NPD4695	Discontinued
0.6556	Remote Similarity	NPD4819	Approved
0.6556	Remote Similarity	NPD4822	Approved
0.6556	Remote Similarity	NPD4820	Approved
0.6542	Remote Similarity	NPD5216	Approved
0.6542	Remote Similarity	NPD6401	Clinical (unspecified phase)
0.6542	Remote Similarity	NPD5215	Approved
0.6542	Remote Similarity	NPD5127	Approved
0.6542	Remote Similarity	NPD5217	Approved
0.6531	Remote Similarity	NPD7748	Approved
0.6526	Remote Similarity	NPD4518	Approved
0.6522	Remote Similarity	NPD5332	Approved
0.6522	Remote Similarity	NPD5362	Discontinued
0.6522	Remote Similarity	NPD5331	Approved
0.6495	Remote Similarity	NPD8034	Phase 2
0.6495	Remote Similarity	NPD8035	Phase 2
0.6484	Remote Similarity	NPD4790	Discontinued
0.6471	Remote Similarity	NPD4747	Approved
0.6458	Remote Similarity	NPD6904	Approved
0.6458	Remote Similarity	NPD6080	Approved
0.6458	Remote Similarity	NPD6673	Approved
0.6437	Remote Similarity	NPD6113	Clinical (unspecified phase)

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