NPASS Compound

Structure

NPC227583 OpenBabel07101718312D 35 38 0 0 1 0 0 0 0 0999 V2000 3.4641 -3.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 7.4106 6.2859 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.7633 6.8212 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.7926 4.3838 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1890 4.5032 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1913 3.4135 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 2.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5981 -3.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7321 -3.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1453 4.9190 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8363 3.9680 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1369 2.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5491 1.1910 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 0.8660 2.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7321 3.0000 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 1.7321 -2.0000 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 -0.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.4325 6.0780 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.1235 5.1270 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 3.8581 3.7601 0.0000 C 0 0 2 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 1.7321 1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5491 2.8090 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 0.8660 1.5000 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 0.8660 -0.5000 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 2.5981 2.5000 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 0.0000 1.0000 0.0000 C 0 0 1 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 -0.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.0000 -1.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.8660 -1.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1 8 1 0 0 0 0 2 21 1 0 0 0 0 3 21 1 0 0 0 0 7 31 1 0 0 0 0 8 9 1 0 0 0 0 9 18 1 0 0 0 0 10 11 2 0 0 0 0 10 22 1 0 0 0 0 11 23 1 0 0 0 0 12 13 1 0 0 0 0 12 26 1 0 0 0 0 13 27 1 0 0 0 0 14 17 1 0 0 0 0 14 24 1 0 0 0 0 15 16 1 0 0 0 0 15 28 1 0 0 0 0 16 30 1 0 0 0 0 17 31 1 0 0 0 0 18 35 1 0 0 0 0 19 25 2 0 0 0 0 19 29 1 0 0 0 0 20 24 1 0 0 0 0 20 32 1 0 0 0 0 21 22 1 0 0 0 0 22 4 1 1 0 0 0 23 5 1 6 0 0 0 23 26 1 0 0 0 0 24 33 1 1 0 0 0 25 27 1 0 0 0 0 25 28 1 0 0 0 0 26 30 1 1 0 0 0 27 30 1 1 0 0 0 28 31 1 1 0 0 0 29 32 1 1 0 0 0 29 35 1 0 0 0 0 30 6 1 1 0 0 0 31 32 1 1 0 0 0 32 34 1 6 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	486.41
Volume:	548.9
LogP:	6.951
LogD:	5.809
LogS:	-6.738
# Rotatable Bonds:	8
TPSA:	49.69
# H-Bond Aceptor:	3
# H-Bond Donor:	2
# Rings:	4
# Heavy Atoms:	3

MedChem Properties

QED Drug-Likeness Score:	0.279
Synthetic Accessibility Score:	5.009
Fsp3:	0.875
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected
GSK Rule:	Rejected
BMS Rule:	0
Golden Triangle Rule:	Rejected
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-4.787
MDCK Permeability:	4.801041359314695e-05
Pgp-inhibitor:	0.918
Pgp-substrate:	0.668
Human Intestinal Absorption (HIA):	0.034
20% Bioavailability (F20%):	0.981
30% Bioavailability (F30%):	0.739

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.037
Plasma Protein Binding (PPB):	88.7814712524414%
Volume Distribution (VD):	1.048
Pgp-substrate:	1.5728799104690552%

ADMET: Metabolism

CYP1A2-inhibitor:	0.049
CYP1A2-substrate:	0.562
CYP2C19-inhibitor:	0.148
CYP2C19-substrate:	0.902
CYP2C9-inhibitor:	0.333
CYP2C9-substrate:	0.048
CYP2D6-inhibitor:	0.012
CYP2D6-substrate:	0.087
CYP3A4-inhibitor:	0.856
CYP3A4-substrate:	0.803

ADMET: Excretion

Clearance (CL):	2.656
Half-life (T1/2):	0.068

ADMET: Toxicity

hERG Blockers:	0.043
Human Hepatotoxicity (H-HT):	0.2
Drug-inuced Liver Injury (DILI):	0.062
AMES Toxicity:	0.004
Rat Oral Acute Toxicity:	0.805
Maximum Recommended Daily Dose:	0.929
Skin Sensitization:	0.042
Carcinogencity:	0.002
Eye Corrosion:	0.004
Eye Irritation:	0.048
Respiratory Toxicity:	0.649

Download Data

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

Natural Product: NPC227583

Natural Product ID:	NPC227583
*Common Name:**	Homaxisterol A3
IUPAC Name:	(3S,5R,6R,9S,10R,13R,14R,17R)-6-butoxy-17-[(E,2R,5R)-5,6-dimethylhept-3-en-2-yl]-10,13-dimethyl-1,2,3,4,6,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthrene-3,5-diol
Synonyms:	Homaxisterol A3
Standard InCHIKey:	REDLNGNAWVGTOL-CBCCXFPSSA-N
Standard InCHI:	InChI=1S/C32H54O3/c1-8-9-18-35-29-19-25-27-13-12-26(23(5)11-10-22(4)21(2)3)30(27,6)16-15-28(25)31(7)17-14-24(33)20-32(29,31)34/h10-11,19,21-24,26-29,33-34H,8-9,12-18,20H2,1-7H3/b11-10+/t22-,23+,24-,26+,27-,28-,29+,30+,31+,32-/m0/s1
SMILES:	CCCCO[C@@H]1C=C2[C@@H]3CC[C@@H]([C@@]3(C)CC[C@@H]2[C@@]2([C@]1(O)C[C@@H](O)CC2)C)[C@@H](/C=C/[C@@H](C(C)C)C)C
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL516384
PubChem CID:	11156004
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000258] Steroids and steroid derivatives [CHEMONTID:0003567] Ergostane steroids [CHEMONTID:0001403] Ergosterols 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
NPO33129	hominaxella sp.	Species	n.a.	n.a.	n.a.	n.a.	n.a.	PMID[15787431]

☑ 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	5

Activity Type	# Activity
Cell Line	5

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT81	Cell Line	A549	Homo sapiens	ED50	=	8.42	ug ml-1	PMID[558971]
NPT146	Cell Line	SK-OV-3	Homo sapiens	ED50	=	7.85	ug ml-1	PMID[558971]
NPT147	Cell Line	SK-MEL-2	Homo sapiens	ED50	=	6.1	ug ml-1	PMID[558971]
NPT574	Cell Line	XF498	Homo sapiens	ED50	=	5.03	ug ml-1	PMID[558971]
NPT393	Cell Line	HCT-116	Homo sapiens	ED50	=	7.1	ug ml-1	PMID[558971]

☑ 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 NPC227583 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	209
0.1-0.2	1366
0.2-0.3	4547
0.3-0.4	10677
0.4-0.5	11710
0.5-0.6	6539
0.6-0.7	5400
0.7-0.8	2025
0.8-0.85	162
0.85-0.9	45
0.9-0.95	10
0.95-1	7

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC12103
1.0	High Similarity	NPC98457
0.9888	High Similarity	NPC8774
0.9775	High Similarity	NPC65402
0.9775	High Similarity	NPC127718
0.956	High Similarity	NPC288970
0.9222	High Similarity	NPC80561
0.9222	High Similarity	NPC329596
0.9222	High Similarity	NPC204188
0.9222	High Similarity	NPC291484
0.9222	High Similarity	NPC3345
0.9222	High Similarity	NPC11216
0.9121	High Similarity	NPC41554
0.9121	High Similarity	NPC97404
0.9111	High Similarity	NPC470361
0.9043	High Similarity	NPC261807
0.8936	High Similarity	NPC103165
0.8936	High Similarity	NPC210717
0.8925	High Similarity	NPC144202
0.89	High Similarity	NPC5475
0.89	High Similarity	NPC284828
0.89	High Similarity	NPC472216
0.89	High Similarity	NPC173905
0.8876	High Similarity	NPC157257
0.8854	High Similarity	NPC473510
0.8817	High Similarity	NPC27531
0.8817	High Similarity	NPC310013
0.8804	High Similarity	NPC295668
0.8791	High Similarity	NPC133588
0.8778	High Similarity	NPC299068
0.8776	High Similarity	NPC474124
0.8764	High Similarity	NPC470077
0.8763	High Similarity	NPC475617
0.8737	High Similarity	NPC72204
0.871	High Similarity	NPC210268
0.87	High Similarity	NPC33053
0.8687	High Similarity	NPC473543
0.8681	High Similarity	NPC149224
0.8673	High Similarity	NPC476471
0.8673	High Similarity	NPC475344
0.8667	High Similarity	NPC470360
0.8667	High Similarity	NPC274448
0.866	High Similarity	NPC230546
0.8646	High Similarity	NPC210337
0.8627	High Similarity	NPC170974
0.8627	High Similarity	NPC191439
0.8627	High Similarity	NPC103627
0.8617	High Similarity	NPC137461
0.8617	High Similarity	NPC307776
0.8602	High Similarity	NPC245410
0.8602	High Similarity	NPC192437
0.8602	High Similarity	NPC270511
0.8602	High Similarity	NPC470390
0.8602	High Similarity	NPC14380
0.8587	High Similarity	NPC474668
0.8586	High Similarity	NPC471887
0.8586	High Similarity	NPC471886
0.8586	High Similarity	NPC471885
0.8586	High Similarity	NPC471888
0.8586	High Similarity	NPC473523
0.8571	High Similarity	NPC261266
0.8571	High Similarity	NPC125399
0.8571	High Similarity	NPC6391
0.8557	High Similarity	NPC476895
0.8544	High Similarity	NPC65034
0.8544	High Similarity	NPC208189
0.8542	High Similarity	NPC88009
0.8539	High Similarity	NPC470049
0.8529	High Similarity	NPC473318
0.8529	High Similarity	NPC28844
0.8529	High Similarity	NPC473328
0.8511	High Similarity	NPC471453
0.8511	High Similarity	NPC114389
0.85	High Similarity	NPC93352
0.8495	Intermediate Similarity	NPC101886
0.8485	Intermediate Similarity	NPC471889
0.8485	Intermediate Similarity	NPC37207
0.8478	Intermediate Similarity	NPC476948
0.8462	Intermediate Similarity	NPC231797
0.8462	Intermediate Similarity	NPC473567
0.8462	Intermediate Similarity	NPC216595
0.8462	Intermediate Similarity	NPC266511
0.8454	Intermediate Similarity	NPC476893
0.8447	Intermediate Similarity	NPC65155
0.8444	Intermediate Similarity	NPC470558
0.8431	Intermediate Similarity	NPC472219
0.8431	Intermediate Similarity	NPC472217
0.8431	Intermediate Similarity	NPC472218
0.8427	Intermediate Similarity	NPC474752
0.8427	Intermediate Similarity	NPC7505
0.8427	Intermediate Similarity	NPC474683
0.8427	Intermediate Similarity	NPC470383
0.8427	Intermediate Similarity	NPC474731
0.8427	Intermediate Similarity	NPC82986
0.8427	Intermediate Similarity	NPC474759
0.8421	Intermediate Similarity	NPC98193
0.8404	Intermediate Similarity	NPC473956
0.8404	Intermediate Similarity	NPC475751
0.84	Intermediate Similarity	NPC471450
0.8387	Intermediate Similarity	NPC471952
0.8387	Intermediate Similarity	NPC212596
0.8387	Intermediate Similarity	NPC4574
0.8384	Intermediate Similarity	NPC476896
0.8384	Intermediate Similarity	NPC285231
0.8384	Intermediate Similarity	NPC21568
0.837	Intermediate Similarity	NPC94462
0.837	Intermediate Similarity	NPC255143
0.8352	Intermediate Similarity	NPC15534
0.8352	Intermediate Similarity	NPC205845
0.8352	Intermediate Similarity	NPC185568
0.8351	Intermediate Similarity	NPC471903
0.835	Intermediate Similarity	NPC128133
0.835	Intermediate Similarity	NPC472901
0.8333	Intermediate Similarity	NPC50964
0.8333	Intermediate Similarity	NPC49964
0.8333	Intermediate Similarity	NPC30166
0.8317	Intermediate Similarity	NPC75608
0.8316	Intermediate Similarity	NPC275671
0.83	Intermediate Similarity	NPC300399
0.83	Intermediate Similarity	NPC471482
0.8298	Intermediate Similarity	NPC109744
0.8298	Intermediate Similarity	NPC138974
0.8286	Intermediate Similarity	NPC477050
0.8283	Intermediate Similarity	NPC38855
0.828	Intermediate Similarity	NPC304083
0.8269	Intermediate Similarity	NPC472215
0.8269	Intermediate Similarity	NPC472214
0.8265	Intermediate Similarity	NPC476021
0.8265	Intermediate Similarity	NPC474994
0.8265	Intermediate Similarity	NPC476040
0.8247	Intermediate Similarity	NPC476894
0.8242	Intermediate Similarity	NPC474634
0.8242	Intermediate Similarity	NPC317458
0.8235	Intermediate Similarity	NPC472898
0.8235	Intermediate Similarity	NPC472899
0.8235	Intermediate Similarity	NPC472900
0.8229	Intermediate Similarity	NPC119379
0.8222	Intermediate Similarity	NPC264245
0.8222	Intermediate Similarity	NPC47761
0.8222	Intermediate Similarity	NPC249423
0.8222	Intermediate Similarity	NPC474531
0.8222	Intermediate Similarity	NPC23852
0.8222	Intermediate Similarity	NPC70927
0.8222	Intermediate Similarity	NPC209620
0.8222	Intermediate Similarity	NPC476646
0.8202	Intermediate Similarity	NPC328714
0.82	Intermediate Similarity	NPC470434
0.8191	Intermediate Similarity	NPC475605
0.8191	Intermediate Similarity	NPC473436
0.8191	Intermediate Similarity	NPC475664
0.8191	Intermediate Similarity	NPC67872
0.819	Intermediate Similarity	NPC470076
0.819	Intermediate Similarity	NPC472987
0.819	Intermediate Similarity	NPC473021
0.8182	Intermediate Similarity	NPC216260
0.8182	Intermediate Similarity	NPC158088
0.8182	Intermediate Similarity	NPC5358
0.8173	Intermediate Similarity	NPC14630
0.8173	Intermediate Similarity	NPC250089
0.8173	Intermediate Similarity	NPC157530
0.8172	Intermediate Similarity	NPC293287
0.8172	Intermediate Similarity	NPC6605
0.8172	Intermediate Similarity	NPC152808
0.8172	Intermediate Similarity	NPC201273
0.8172	Intermediate Similarity	NPC269058
0.8172	Intermediate Similarity	NPC71520
0.8152	Intermediate Similarity	NPC83702
0.8152	Intermediate Similarity	NPC124172
0.8152	Intermediate Similarity	NPC474047
0.8144	Intermediate Similarity	NPC477605
0.8137	Intermediate Similarity	NPC470885
0.8137	Intermediate Similarity	NPC187400
0.8137	Intermediate Similarity	NPC221562
0.8132	Intermediate Similarity	NPC296701
0.8132	Intermediate Similarity	NPC471408
0.8132	Intermediate Similarity	NPC155521
0.8132	Intermediate Similarity	NPC101462
0.8132	Intermediate Similarity	NPC87489
0.8132	Intermediate Similarity	NPC218616
0.8125	Intermediate Similarity	NPC234335
0.8125	Intermediate Similarity	NPC177641
0.8119	Intermediate Similarity	NPC136816
0.8113	Intermediate Similarity	NPC475354
0.8111	Intermediate Similarity	NPC234193
0.8111	Intermediate Similarity	NPC164840
0.8111	Intermediate Similarity	NPC241290
0.8111	Intermediate Similarity	NPC13554
0.8111	Intermediate Similarity	NPC96362
0.8111	Intermediate Similarity	NPC236112
0.8111	Intermediate Similarity	NPC209944
0.8111	Intermediate Similarity	NPC287749
0.8105	Intermediate Similarity	NPC97103
0.8105	Intermediate Similarity	NPC115607
0.8105	Intermediate Similarity	NPC105495
0.81	Intermediate Similarity	NPC469942
0.809	Intermediate Similarity	NPC87604
0.8085	Intermediate Similarity	NPC474657
0.8085	Intermediate Similarity	NPC470620
0.8085	Intermediate Similarity	NPC186145
0.8085	Intermediate Similarity	NPC189777

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 NPC227583 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	188
0.1-0.2	1517
0.2-0.3	4009
0.3-0.4	2271
0.4-0.5	701
0.5-0.6	221
0.6-0.7	178
0.7-0.8	63
0.8-0.85	2
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.8085	Intermediate Similarity	NPD7524	Approved
0.7957	Intermediate Similarity	NPD7338	Clinical (unspecified phase)
0.7912	Intermediate Similarity	NPD7525	Registered
0.7849	Intermediate Similarity	NPD6695	Phase 3
0.7753	Intermediate Similarity	NPD7339	Approved
0.7753	Intermediate Similarity	NPD6942	Approved
0.7717	Intermediate Similarity	NPD6931	Approved
0.7717	Intermediate Similarity	NPD7514	Phase 3
0.7717	Intermediate Similarity	NPD6930	Phase 2
0.7708	Intermediate Similarity	NPD7750	Discontinued
0.7708	Intermediate Similarity	NPD4751	Clinical (unspecified phase)
0.767	Intermediate Similarity	NPD4159	Approved
0.7609	Intermediate Similarity	NPD6929	Approved
0.7589	Intermediate Similarity	NPD7328	Approved
0.7589	Intermediate Similarity	NPD7327	Approved
0.7582	Intermediate Similarity	NPD6932	Approved
0.7544	Intermediate Similarity	NPD8296	Approved
0.7544	Intermediate Similarity	NPD8033	Approved
0.7544	Intermediate Similarity	NPD8380	Approved
0.7544	Intermediate Similarity	NPD8335	Approved
0.7544	Intermediate Similarity	NPD8379	Approved
0.7544	Intermediate Similarity	NPD8378	Approved
0.7527	Intermediate Similarity	NPD7332	Phase 2
0.7522	Intermediate Similarity	NPD7516	Approved
0.75	Intermediate Similarity	NPD7145	Approved
0.75	Intermediate Similarity	NPD7115	Discovery
0.7476	Intermediate Similarity	NPD7638	Approved
0.7473	Intermediate Similarity	NPD3701	Clinical (unspecified phase)
0.7473	Intermediate Similarity	NPD6933	Approved
0.7456	Intermediate Similarity	NPD8294	Approved
0.7456	Intermediate Similarity	NPD8377	Approved
0.7447	Intermediate Similarity	NPD6902	Approved
0.7419	Intermediate Similarity	NPD7645	Phase 2
0.7404	Intermediate Similarity	NPD7640	Approved
0.7404	Intermediate Similarity	NPD7639	Approved
0.7391	Intermediate Similarity	NPD5776	Phase 2
0.7391	Intermediate Similarity	NPD6925	Approved
0.7391	Intermediate Similarity	NPD7503	Approved
0.732	Intermediate Similarity	NPD6893	Approved
0.7253	Intermediate Similarity	NPD6924	Approved
0.7253	Intermediate Similarity	NPD4785	Approved
0.7253	Intermediate Similarity	NPD4784	Approved
0.7253	Intermediate Similarity	NPD6926	Approved
0.7234	Intermediate Similarity	NPD6683	Phase 2
0.7228	Intermediate Similarity	NPD7087	Discontinued
0.7216	Intermediate Similarity	NPD4786	Approved
0.7182	Intermediate Similarity	NPD4061	Clinical (unspecified phase)
0.717	Intermediate Similarity	NPD5344	Discontinued
0.7143	Intermediate Similarity	NPD8297	Approved
0.7143	Intermediate Similarity	NPD4225	Approved
0.7083	Intermediate Similarity	NPD6898	Phase 1
0.7059	Intermediate Similarity	NPD6079	Approved
0.7059	Intermediate Similarity	NPD7637	Suspended
0.7033	Intermediate Similarity	NPD7151	Approved
0.7033	Intermediate Similarity	NPD7152	Approved
0.7033	Intermediate Similarity	NPD7150	Approved
0.7033	Intermediate Similarity	NPD4243	Approved
0.703	Intermediate Similarity	NPD6051	Approved
0.703	Intermediate Similarity	NPD5328	Approved
0.701	Intermediate Similarity	NPD3667	Approved
0.7	Intermediate Similarity	NPD7507	Approved
0.699	Remote Similarity	NPD6399	Phase 3
0.699	Remote Similarity	NPD4202	Approved
0.6989	Remote Similarity	NPD8264	Approved
0.6979	Remote Similarity	NPD7509	Discontinued
0.6979	Remote Similarity	NPD4748	Discontinued
0.6967	Remote Similarity	NPD7319	Approved
0.6964	Remote Similarity	NPD4634	Approved
0.6947	Remote Similarity	NPD7322	Clinical (unspecified phase)
0.6944	Remote Similarity	NPD5211	Phase 2
0.6937	Remote Similarity	NPD6899	Approved
0.6937	Remote Similarity	NPD6881	Approved
0.693	Remote Similarity	NPD4632	Approved
0.6923	Remote Similarity	NPD7143	Approved
0.6923	Remote Similarity	NPD7144	Approved
0.6916	Remote Similarity	NPD5285	Approved
0.6916	Remote Similarity	NPD5286	Approved
0.6916	Remote Similarity	NPD4696	Approved
0.6909	Remote Similarity	NPD7128	Approved
0.6909	Remote Similarity	NPD5739	Approved
0.6909	Remote Similarity	NPD6675	Approved
0.6909	Remote Similarity	NPD6640	Phase 3
0.6909	Remote Similarity	NPD6402	Approved
0.6903	Remote Similarity	NPD8130	Phase 1
0.69	Remote Similarity	NPD3618	Phase 1
0.6887	Remote Similarity	NPD4755	Approved
0.6864	Remote Similarity	NPD6319	Approved
0.6864	Remote Similarity	NPD6054	Approved
0.6847	Remote Similarity	NPD5697	Approved
0.6847	Remote Similarity	NPD6412	Phase 2
0.6818	Remote Similarity	NPD5141	Approved
0.6814	Remote Similarity	NPD7102	Approved
0.6814	Remote Similarity	NPD6883	Approved
0.6814	Remote Similarity	NPD7290	Approved
0.6814	Remote Similarity	NPD5955	Clinical (unspecified phase)
0.6813	Remote Similarity	NPD4267	Clinical (unspecified phase)
0.6813	Remote Similarity	NPD6923	Approved
0.6813	Remote Similarity	NPD6922	Approved
0.6789	Remote Similarity	NPD5224	Approved
0.6789	Remote Similarity	NPD5226	Approved
0.6789	Remote Similarity	NPD7632	Discontinued
0.6789	Remote Similarity	NPD4633	Approved
0.6789	Remote Similarity	NPD5225	Approved
0.6786	Remote Similarity	NPD5345	Clinical (unspecified phase)
0.6786	Remote Similarity	NPD7320	Approved
0.6786	Remote Similarity	NPD6686	Approved
0.6783	Remote Similarity	NPD8133	Approved
0.6759	Remote Similarity	NPD6648	Approved
0.6759	Remote Similarity	NPD4700	Approved
0.6754	Remote Similarity	NPD6617	Approved
0.6754	Remote Similarity	NPD6869	Approved
0.6754	Remote Similarity	NPD6649	Approved
0.6754	Remote Similarity	NPD6847	Approved
0.6754	Remote Similarity	NPD6650	Approved
0.675	Remote Similarity	NPD6370	Approved
0.6727	Remote Similarity	NPD5174	Approved
0.6727	Remote Similarity	NPD5175	Approved
0.6726	Remote Similarity	NPD6373	Approved
0.6726	Remote Similarity	NPD6014	Approved
0.6726	Remote Similarity	NPD6372	Approved
0.6726	Remote Similarity	NPD6013	Approved
0.6726	Remote Similarity	NPD6012	Approved
0.6723	Remote Similarity	NPD7741	Discontinued
0.6723	Remote Similarity	NPD6059	Approved
0.6701	Remote Similarity	NPD4195	Approved
0.6697	Remote Similarity	NPD5223	Approved
0.6696	Remote Similarity	NPD5701	Approved
0.6696	Remote Similarity	NPD6882	Approved
0.6667	Remote Similarity	NPD6016	Approved
0.6667	Remote Similarity	NPD6015	Approved
0.6639	Remote Similarity	NPD7492	Approved
0.6637	Remote Similarity	NPD6011	Approved
0.6636	Remote Similarity	NPD5222	Approved
0.6636	Remote Similarity	NPD5220	Clinical (unspecified phase)
0.6636	Remote Similarity	NPD5221	Approved
0.6632	Remote Similarity	NPD5275	Approved
0.6632	Remote Similarity	NPD4190	Phase 3
0.6613	Remote Similarity	NPD7736	Approved
0.6612	Remote Similarity	NPD5988	Approved
0.661	Remote Similarity	NPD6009	Approved
0.6585	Remote Similarity	NPD6616	Approved
0.6574	Remote Similarity	NPD5173	Approved
0.6574	Remote Similarity	NPD6084	Phase 2
0.6574	Remote Similarity	NPD6083	Phase 2
0.6571	Remote Similarity	NPD8035	Phase 2
0.6571	Remote Similarity	NPD8034	Phase 2
0.6557	Remote Similarity	NPD7604	Phase 2
0.6552	Remote Similarity	NPD6053	Discontinued
0.6549	Remote Similarity	NPD5954	Clinical (unspecified phase)
0.6538	Remote Similarity	NPD4753	Phase 2
0.6535	Remote Similarity	NPD3666	Approved
0.6535	Remote Similarity	NPD3133	Approved
0.6535	Remote Similarity	NPD3665	Phase 1
0.6532	Remote Similarity	NPD8293	Discontinued
0.6532	Remote Similarity	NPD7078	Approved
0.6529	Remote Similarity	NPD5983	Phase 2
0.6491	Remote Similarity	NPD4730	Approved
0.6491	Remote Similarity	NPD4729	Approved
0.6481	Remote Similarity	NPD4697	Phase 3
0.6476	Remote Similarity	NPD7838	Discovery
0.6476	Remote Similarity	NPD7136	Phase 2
0.6471	Remote Similarity	NPD7520	Clinical (unspecified phase)
0.6466	Remote Similarity	NPD6401	Clinical (unspecified phase)
0.646	Remote Similarity	NPD4767	Approved
0.646	Remote Similarity	NPD4768	Approved
0.646	Remote Similarity	NPD6008	Approved
0.6452	Remote Similarity	NPD6336	Discontinued
0.6449	Remote Similarity	NPD7748	Approved
0.6435	Remote Similarity	NPD8132	Clinical (unspecified phase)
0.6429	Remote Similarity	NPD4754	Approved
0.6422	Remote Similarity	NPD7902	Approved
0.6393	Remote Similarity	NPD8516	Approved
0.6393	Remote Similarity	NPD8517	Approved
0.6393	Remote Similarity	NPD8515	Approved
0.6393	Remote Similarity	NPD8513	Phase 3
0.6389	Remote Similarity	NPD5210	Approved
0.6389	Remote Similarity	NPD4629	Approved
0.6379	Remote Similarity	NPD5250	Approved
0.6379	Remote Similarity	NPD5249	Phase 3
0.6379	Remote Similarity	NPD5248	Approved
0.6379	Remote Similarity	NPD5247	Approved
0.6379	Remote Similarity	NPD5251	Approved
0.6373	Remote Similarity	NPD3668	Phase 3
0.6364	Remote Similarity	NPD5290	Discontinued
0.6364	Remote Similarity	NPD7101	Approved
0.6364	Remote Similarity	NPD7100	Approved
0.6348	Remote Similarity	NPD5128	Approved
0.6337	Remote Similarity	NPD4221	Approved
0.6337	Remote Similarity	NPD4223	Phase 3
0.6325	Remote Similarity	NPD5216	Approved
0.6325	Remote Similarity	NPD5215	Approved
0.6325	Remote Similarity	NPD5217	Approved
0.6321	Remote Similarity	NPD3168	Discontinued
0.6311	Remote Similarity	NPD5329	Approved
0.6281	Remote Similarity	NPD6335	Approved
0.6264	Remote Similarity	NPD371	Approved
0.6262	Remote Similarity	NPD7515	Phase 2
0.625	Remote Similarity	NPD7334	Approved
0.625	Remote Similarity	NPD5279	Phase 3
0.625	Remote Similarity	NPD5330	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