NPASS Compound

Structure

CID189908 OpenBabel06191715572D 27 28 0 0 1 0 0 0 0 0999 V2000 7.6353 -0.7071 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 8.5013 0.7929 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7765 -2.8978 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2588 0.9659 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8978 -0.7765 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7615 0.6670 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4392 0.2929 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3052 -1.2071 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3052 0.7929 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1712 -0.7071 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.7693 0.7929 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.9033 0.2929 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5731 -1.2071 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 7.6353 0.2929 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4392 -0.7071 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1712 0.2929 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9659 -0.2588 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2247 -1.2247 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 0.4483 -1.6730 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7071 -0.7071 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.5176 -1.9319 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 0.0000 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -1.6730 0.4483 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.1554 -2.3801 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 5.0372 0.7929 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.1907 -1.4836 0.0000 S 0 0 0 0 0 0 0 0 0 0 0 0 0.8376 0.2843 0.0000 S 0 0 0 0 0 0 0 0 0 0 0 0 1 14 1 0 0 0 0 2 14 1 0 0 0 0 3 21 1 0 0 0 0 4 22 1 0 0 0 0 5 26 1 0 0 0 0 6 27 1 0 0 0 0 7 9 1 0 0 0 0 7 15 2 0 0 0 0 8 10 2 0 0 0 0 8 15 1 0 0 0 0 9 16 2 0 0 0 0 10 16 1 0 0 0 0 11 12 1 0 0 0 0 11 14 2 0 0 0 0 12 25 1 0 0 0 0 13 15 1 0 0 0 0 16 25 1 0 0 0 0 17 18 1 0 0 0 0 17 22 1 0 0 0 0 17 23 2 0 0 0 0 18 21 1 0 0 0 0 18 26 1 6 0 0 0 19 20 1 0 0 0 0 19 21 1 0 0 0 0 19 24 2 0 0 0 0 20 13 1 1 0 0 0 20 22 1 0 0 0 0 20 27 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	408.15
Volume:	406.927
LogP:	4.15
LogD:	2.844
LogS:	-4.572
# Rotatable Bonds:	7
TPSA:	49.85
# H-Bond Aceptor:	5
# H-Bond Donor:	0
# Rings:	2
# Heavy Atoms:	7

MedChem Properties

QED Drug-Likeness Score:	0.648
Synthetic Accessibility Score:	4.061
Fsp3:	0.5
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected
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:	-4.667
MDCK Permeability:	2.5262776034651324e-05
Pgp-inhibitor:	0.972
Pgp-substrate:	0.43
Human Intestinal Absorption (HIA):	0.411
20% Bioavailability (F20%):	0.012
30% Bioavailability (F30%):	0.033

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.674
Plasma Protein Binding (PPB):	96.903564453125%
Volume Distribution (VD):	1.384
Pgp-substrate:	2.7116239070892334%

ADMET: Metabolism

CYP1A2-inhibitor:	0.141
CYP1A2-substrate:	0.557
CYP2C19-inhibitor:	0.958
CYP2C19-substrate:	0.94
CYP2C9-inhibitor:	0.956
CYP2C9-substrate:	0.703
CYP2D6-inhibitor:	0.078
CYP2D6-substrate:	0.207
CYP3A4-inhibitor:	0.796
CYP3A4-substrate:	0.946

ADMET: Excretion

Clearance (CL):	11.427
Half-life (T1/2):	0.517

ADMET: Toxicity

hERG Blockers:	0.008
Human Hepatotoxicity (H-HT):	0.826
Drug-inuced Liver Injury (DILI):	0.957
AMES Toxicity:	0.038
Rat Oral Acute Toxicity:	0.045
Maximum Recommended Daily Dose:	0.063
Skin Sensitization:	0.362
Carcinogencity:	0.483
Eye Corrosion:	0.003
Eye Irritation:	0.008
Respiratory Toxicity:	0.003

Download Data

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

Natural Product: NPC189908

Natural Product ID:	NPC189908
*Common Name:**	Cis-Bis(Methylthio)Silvatin
IUPAC Name:	(3R,6R)-1,4-dimethyl-3-[[4-(3-methylbut-2-enoxy)phenyl]methyl]-3,6-bis(methylsulfanyl)piperazine-2,5-dione
Synonyms:	Cis-Bis(Methylthio)Silvatin
Standard InCHIKey:	XBKBUMFBHNQOLC-UYAOXDASSA-N
Standard InCHI:	InChI=1S/C20H28N2O3S2/c1-14(2)11-12-25-16-9-7-15(8-10-16)13-20(27-6)19(24)21(3)18(26-5)17(23)22(20)4/h7-11,18H,12-13H2,1-6H3/t18-,20-/m1/s1
SMILES:	CS[C@H]1N(C)C(=O)[C@](N(C1=O)C)(SC)Cc1ccc(cc1)OCC=C(C)C
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL253544
PubChem CID:	11069575
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000264] Organic acids and derivatives [CHEMONTID:0000265] Carboxylic acids and derivatives [CHEMONTID:0000013] Amino acids, peptides, and analogues [CHEMONTID:0000347] Amino acids and derivatives [CHEMONTID:0000060] Alpha amino acids 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
NPO33373	penicillium spp.	Species	Aspergillaceae	Eukaryota	n.a.	Australian	n.a.	PMID[17958395]
NPO19935	Evodia rutaecarpa	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[7463094]
NPO19935	Evodia rutaecarpa	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[8201313]
NPO19935	Evodia rutaecarpa	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[8699182]
NPO1879	Feijoa sellowiana	Species	Myrtaceae	Eukaryota	Fruit	n.a.	n.a.	Database[FooDB]
NPO1879	Feijoa sellowiana	Species	Myrtaceae	Eukaryota		n.a.	n.a.	Database[FooDB]
NPO19935	Evodia rutaecarpa	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO1879	Feijoa sellowiana	Species	Myrtaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO33	Coriolus consors	Species	Coriolaceae	Eukaryota	n.a.	n.a.	n.a.	Database[Title]
NPO19935	Evodia rutaecarpa	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO22444	Ceramium boydenii	Species	Ceramiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO19935	Evodia rutaecarpa	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO3772	Athrixia angustissima	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO2813	Chrysanthemum fuscatum	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO1879	Feijoa sellowiana	Species	Myrtaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO6585	Petromyzon fluviatilis	Species	Petromyzontidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO33	Coriolus consors	Species	Coriolaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO956	Tectaria subtriphylla	Species	Tectariaceae	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
Others	1

Activity Type	# Activity
NON-MOLECULAR	1

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT20529	NON-MOLECULAR	NON-PROTEIN TARGET	n.a.	LD99	=	0.15	uM	PMID[485544]

☑ 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 NPC189908 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	206
0.1-0.2	1731
0.2-0.3	8153
0.3-0.4	9945
0.4-0.5	8354
0.5-0.6	13214
0.6-0.7	1036
0.7-0.8	56
0.8-0.85	1
0.85-0.9	0
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
0.8207	Intermediate Similarity	NPC307682
0.7847	Intermediate Similarity	NPC283079
0.774	Intermediate Similarity	NPC257390
0.7677	Intermediate Similarity	NPC324081
0.7662	Intermediate Similarity	NPC9373
0.7635	Intermediate Similarity	NPC266425
0.763	Intermediate Similarity	NPC477526
0.7457	Intermediate Similarity	NPC4910
0.7457	Intermediate Similarity	NPC329731
0.7453	Intermediate Similarity	NPC287757
0.7453	Intermediate Similarity	NPC319320
0.745	Intermediate Similarity	NPC470392
0.7434	Intermediate Similarity	NPC225745
0.74	Intermediate Similarity	NPC132308
0.7397	Intermediate Similarity	NPC124776
0.7368	Intermediate Similarity	NPC106606
0.7347	Intermediate Similarity	NPC218323
0.7303	Intermediate Similarity	NPC196708
0.7303	Intermediate Similarity	NPC180647
0.7278	Intermediate Similarity	NPC164608
0.7229	Intermediate Similarity	NPC254700
0.7207	Intermediate Similarity	NPC184933
0.7207	Intermediate Similarity	NPC59827
0.7186	Intermediate Similarity	NPC473502
0.7169	Intermediate Similarity	NPC472923
0.7143	Intermediate Similarity	NPC469505
0.711	Intermediate Similarity	NPC32064
0.7103	Intermediate Similarity	NPC302169
0.7101	Intermediate Similarity	NPC196091
0.7097	Intermediate Similarity	NPC28641
0.7097	Intermediate Similarity	NPC194359
0.7092	Intermediate Similarity	NPC26524
0.7088	Intermediate Similarity	NPC477527
0.7063	Intermediate Similarity	NPC296085
0.7059	Intermediate Similarity	NPC169766
0.7051	Intermediate Similarity	NPC231572
0.7041	Intermediate Similarity	NPC186617
0.7025	Intermediate Similarity	NPC308571
0.7024	Intermediate Similarity	NPC469479
0.7006	Intermediate Similarity	NPC276120
0.7	Intermediate Similarity	NPC473693
0.7	Intermediate Similarity	NPC471568
0.6987	Remote Similarity	NPC252107
0.6986	Remote Similarity	NPC321133
0.6986	Remote Similarity	NPC263835
0.697	Remote Similarity	NPC471649
0.6957	Remote Similarity	NPC71629
0.6954	Remote Similarity	NPC475421
0.6949	Remote Similarity	NPC315542
0.6949	Remote Similarity	NPC138083
0.6949	Remote Similarity	NPC102760
0.6923	Remote Similarity	NPC242159
0.6923	Remote Similarity	NPC99078
0.6923	Remote Similarity	NPC313694
0.6913	Remote Similarity	NPC328267
0.6903	Remote Similarity	NPC29650
0.6899	Remote Similarity	NPC470709
0.6879	Remote Similarity	NPC470707
0.6879	Remote Similarity	NPC220923
0.6875	Remote Similarity	NPC81026
0.6862	Remote Similarity	NPC477666
0.6861	Remote Similarity	NPC298224
0.6859	Remote Similarity	NPC73883
0.6859	Remote Similarity	NPC255817
0.6859	Remote Similarity	NPC230698
0.6859	Remote Similarity	NPC136330
0.6859	Remote Similarity	NPC196609
0.6859	Remote Similarity	NPC205178
0.6859	Remote Similarity	NPC251454
0.6859	Remote Similarity	NPC277042
0.6859	Remote Similarity	NPC138365
0.6849	Remote Similarity	NPC293424
0.6848	Remote Similarity	NPC119669
0.6842	Remote Similarity	NPC471651
0.6836	Remote Similarity	NPC470112
0.6836	Remote Similarity	NPC470903
0.6836	Remote Similarity	NPC167763
0.6835	Remote Similarity	NPC150712
0.6835	Remote Similarity	NPC40321
0.6832	Remote Similarity	NPC16188
0.6829	Remote Similarity	NPC470088
0.6824	Remote Similarity	NPC471396
0.6813	Remote Similarity	NPC471680
0.6813	Remote Similarity	NPC266741
0.6812	Remote Similarity	NPC38209
0.6809	Remote Similarity	NPC259554
0.68	Remote Similarity	NPC255253
0.6796	Remote Similarity	NPC29531
0.6796	Remote Similarity	NPC64140
0.6796	Remote Similarity	NPC174122
0.6795	Remote Similarity	NPC473360
0.6795	Remote Similarity	NPC167096
0.6793	Remote Similarity	NPC149962
0.6792	Remote Similarity	NPC212850
0.6792	Remote Similarity	NPC189724
0.6792	Remote Similarity	NPC83289
0.6786	Remote Similarity	NPC476443
0.6786	Remote Similarity	NPC133817
0.6774	Remote Similarity	NPC318862
0.6772	Remote Similarity	NPC257511
0.6768	Remote Similarity	NPC233702
0.6766	Remote Similarity	NPC56635
0.6763	Remote Similarity	NPC473855
0.676	Remote Similarity	NPC299806
0.6759	Remote Similarity	NPC51345
0.6758	Remote Similarity	NPC473407
0.6758	Remote Similarity	NPC473378
0.6757	Remote Similarity	NPC144314
0.6744	Remote Similarity	NPC315388
0.674	Remote Similarity	NPC234069
0.6738	Remote Similarity	NPC97811
0.6731	Remote Similarity	NPC325568
0.6726	Remote Similarity	NPC169742
0.6724	Remote Similarity	NPC306804
0.6724	Remote Similarity	NPC137627
0.6723	Remote Similarity	NPC153554
0.672	Remote Similarity	NPC50548
0.6714	Remote Similarity	NPC1065
0.6711	Remote Similarity	NPC320242
0.6705	Remote Similarity	NPC206941
0.6704	Remote Similarity	NPC302235
0.6689	Remote Similarity	NPC472888
0.6689	Remote Similarity	NPC43275
0.6687	Remote Similarity	NPC471647
0.6687	Remote Similarity	NPC471646
0.6687	Remote Similarity	NPC469978
0.6687	Remote Similarity	NPC39431
0.6686	Remote Similarity	NPC107938
0.6686	Remote Similarity	NPC155506
0.6686	Remote Similarity	NPC294516
0.6686	Remote Similarity	NPC279871
0.6686	Remote Similarity	NPC159767
0.6684	Remote Similarity	NPC123859
0.6667	Remote Similarity	NPC473007
0.6667	Remote Similarity	NPC214239
0.6667	Remote Similarity	NPC118419
0.6667	Remote Similarity	NPC305717
0.6667	Remote Similarity	NPC248822
0.6649	Remote Similarity	NPC471563
0.6649	Remote Similarity	NPC242728
0.6646	Remote Similarity	NPC109580
0.6645	Remote Similarity	NPC160193
0.6645	Remote Similarity	NPC120251
0.6643	Remote Similarity	NPC42383
0.6643	Remote Similarity	NPC470393
0.6643	Remote Similarity	NPC95977
0.6643	Remote Similarity	NPC473418
0.663	Remote Similarity	NPC149571
0.663	Remote Similarity	NPC204970
0.6627	Remote Similarity	NPC202198
0.6627	Remote Similarity	NPC262166
0.6626	Remote Similarity	NPC247298
0.6625	Remote Similarity	NPC259800
0.6625	Remote Similarity	NPC318984
0.6625	Remote Similarity	NPC241086
0.6625	Remote Similarity	NPC318028
0.6625	Remote Similarity	NPC328137
0.6625	Remote Similarity	NPC128877
0.6625	Remote Similarity	NPC317741
0.6625	Remote Similarity	NPC282087
0.6623	Remote Similarity	NPC469666
0.6623	Remote Similarity	NPC172403
0.6615	Remote Similarity	NPC477665
0.6609	Remote Similarity	NPC40234
0.6609	Remote Similarity	NPC475204
0.6609	Remote Similarity	NPC475123
0.6609	Remote Similarity	NPC46009
0.6607	Remote Similarity	NPC203424
0.6607	Remote Similarity	NPC206372
0.6604	Remote Similarity	NPC145446
0.6604	Remote Similarity	NPC137172
0.6601	Remote Similarity	NPC110131
0.6599	Remote Similarity	NPC19290
0.6597	Remote Similarity	NPC233238
0.6591	Remote Similarity	NPC476227
0.6584	Remote Similarity	NPC314682
0.6584	Remote Similarity	NPC251439
0.6579	Remote Similarity	NPC217277
0.6579	Remote Similarity	NPC211218
0.6577	Remote Similarity	NPC256369
0.6577	Remote Similarity	NPC264976
0.6575	Remote Similarity	NPC252004
0.6573	Remote Similarity	NPC269750
0.6573	Remote Similarity	NPC234639
0.6573	Remote Similarity	NPC194671
0.6571	Remote Similarity	NPC108875
0.6571	Remote Similarity	NPC38079
0.6571	Remote Similarity	NPC230611
0.657	Remote Similarity	NPC135006
0.657	Remote Similarity	NPC158900
0.657	Remote Similarity	NPC475780
0.6568	Remote Similarity	NPC323336
0.6568	Remote Similarity	NPC326349
0.6562	Remote Similarity	NPC95366
0.6562	Remote Similarity	NPC248505
0.6561	Remote Similarity	NPC247018
0.6561	Remote Similarity	NPC307123
0.6561	Remote Similarity	NPC274732
0.6561	Remote Similarity	NPC97870
0.6556	Remote Similarity	NPC26285

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 NPC189908 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	142
0.1-0.2	663
0.2-0.3	960
0.3-0.4	1836
0.4-0.5	2805
0.5-0.6	2019
0.6-0.7	676
0.7-0.8	48
0.8-0.85	1
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.8039	Intermediate Similarity	NPD7131	Phase 3
0.7917	Intermediate Similarity	NPD5746	Approved
0.7877	Intermediate Similarity	NPD3142	Approved
0.7877	Intermediate Similarity	NPD3140	Approved
0.7808	Intermediate Similarity	NPD2245	Discovery
0.7808	Intermediate Similarity	NPD5745	Approved
0.7785	Intermediate Similarity	NPD5355	Approved
0.7785	Intermediate Similarity	NPD5356	Approved
0.7516	Intermediate Similarity	NPD6390	Discontinued
0.75	Intermediate Similarity	NPD1725	Approved
0.7469	Intermediate Similarity	NPD5967	Approved
0.7456	Intermediate Similarity	NPD5484	Approved
0.7456	Intermediate Similarity	NPD5485	Approved
0.7451	Intermediate Similarity	NPD5085	Clinical (unspecified phase)
0.7407	Intermediate Similarity	NPD6668	Clinical (unspecified phase)
0.7383	Intermediate Similarity	NPD3374	Clinical (unspecified phase)
0.732	Intermediate Similarity	NPD3693	Clinical (unspecified phase)
0.7305	Intermediate Similarity	NPD7608	Discontinued
0.7273	Intermediate Similarity	NPD5114	Approved
0.7273	Intermediate Similarity	NPD5113	Approved
0.7273	Intermediate Similarity	NPD6382	Discontinued
0.7273	Intermediate Similarity	NPD5112	Approved
0.7267	Intermediate Similarity	NPD2052	Approved
0.7257	Intermediate Similarity	NPD4434	Approved
0.7257	Intermediate Similarity	NPD6089	Clinical (unspecified phase)
0.7232	Intermediate Similarity	NPD6505	Approved
0.7232	Intermediate Similarity	NPD5994	Discontinued
0.7232	Intermediate Similarity	NPD6504	Approved
0.7222	Intermediate Similarity	NPD2053	Approved
0.7222	Intermediate Similarity	NPD22	Approved
0.7219	Intermediate Similarity	NPD3058	Clinical (unspecified phase)
0.7216	Intermediate Similarity	NPD4435	Approved
0.7211	Intermediate Similarity	NPD7258	Clinical (unspecified phase)
0.7183	Intermediate Similarity	NPD3596	Phase 2
0.7178	Intermediate Similarity	NPD7109	Clinical (unspecified phase)
0.7178	Intermediate Similarity	NPD7110	Phase 1
0.7178	Intermediate Similarity	NPD2513	Approved
0.7162	Intermediate Similarity	NPD4098	Discontinued
0.7152	Intermediate Similarity	NPD5718	Phase 2
0.7143	Intermediate Similarity	NPD5688	Approved
0.7143	Intermediate Similarity	NPD7484	Phase 3
0.7143	Intermediate Similarity	NPD6662	Clinical (unspecified phase)
0.7143	Intermediate Similarity	NPD5689	Approved
0.7143	Intermediate Similarity	NPD7485	Phase 3
0.7134	Intermediate Similarity	NPD3007	Approved
0.7134	Intermediate Similarity	NPD2976	Clinical (unspecified phase)
0.7134	Intermediate Similarity	NPD2515	Approved
0.7133	Intermediate Similarity	NPD5752	Clinical (unspecified phase)
0.7126	Intermediate Similarity	NPD6862	Phase 2
0.7126	Intermediate Similarity	NPD7132	Clinical (unspecified phase)
0.7124	Intermediate Similarity	NPD4618	Approved
0.7124	Intermediate Similarity	NPD4622	Approved
0.7117	Intermediate Similarity	NPD1337	Clinical (unspecified phase)
0.7099	Intermediate Similarity	NPD4124	Clinical (unspecified phase)
0.7097	Intermediate Similarity	NPD3152	Clinical (unspecified phase)
0.7095	Intermediate Similarity	NPD3479	Discontinued
0.7083	Intermediate Similarity	NPD3861	Approved
0.7083	Intermediate Similarity	NPD2486	Discontinued
0.7083	Intermediate Similarity	NPD2904	Discontinued
0.7083	Intermediate Similarity	NPD3862	Approved
0.7081	Intermediate Similarity	NPD1975	Clinical (unspecified phase)
0.7051	Intermediate Similarity	NPD2239	Approved
0.7051	Intermediate Similarity	NPD4476	Approved
0.7051	Intermediate Similarity	NPD2240	Approved
0.7051	Intermediate Similarity	NPD4477	Approved
0.7045	Intermediate Similarity	NPD6851	Approved
0.7045	Intermediate Similarity	NPD6853	Approved
0.7041	Intermediate Similarity	NPD2516	Approved
0.7037	Intermediate Similarity	NPD7427	Discontinued
0.7034	Intermediate Similarity	NPD2595	Approved
0.7034	Intermediate Similarity	NPD2594	Approved
0.7032	Intermediate Similarity	NPD743	Approved
0.7019	Intermediate Similarity	NPD3146	Approved
0.7019	Intermediate Similarity	NPD3688	Clinical (unspecified phase)
0.7011	Intermediate Similarity	NPD6297	Approved
0.7006	Intermediate Similarity	NPD5865	Clinical (unspecified phase)
0.7	Intermediate Similarity	NPD160	Clinical (unspecified phase)
0.7	Intermediate Similarity	NPD2517	Approved
0.6987	Remote Similarity	NPD3846	Clinical (unspecified phase)
0.6986	Remote Similarity	NPD2668	Approved
0.6986	Remote Similarity	NPD2423	Clinical (unspecified phase)
0.6986	Remote Similarity	NPD2667	Approved
0.6982	Remote Similarity	NPD2042	Clinical (unspecified phase)
0.6982	Remote Similarity	NPD2041	Clinical (unspecified phase)
0.6975	Remote Similarity	NPD7303	Discontinued
0.6974	Remote Similarity	NPD5163	Phase 2
0.6972	Remote Similarity	NPD1241	Discontinued
0.6966	Remote Similarity	NPD6581	Approved
0.6966	Remote Similarity	NPD6580	Approved
0.6964	Remote Similarity	NPD8031	Discontinued
0.6962	Remote Similarity	NPD3655	Clinical (unspecified phase)
0.6962	Remote Similarity	NPD7596	Clinical (unspecified phase)
0.6957	Remote Similarity	NPD5297	Approved
0.6946	Remote Similarity	NPD2097	Approved
0.6941	Remote Similarity	NPD5262	Discontinued
0.694	Remote Similarity	NPD5564	Approved
0.6939	Remote Similarity	NPD3294	Phase 2
0.6939	Remote Similarity	NPD3447	Discontinued
0.6933	Remote Similarity	NPD5586	Clinical (unspecified phase)
0.6928	Remote Similarity	NPD7577	Discontinued
0.6928	Remote Similarity	NPD7317	Phase 3
0.6923	Remote Similarity	NPD2200	Suspended
0.6918	Remote Similarity	NPD6830	Clinical (unspecified phase)
0.6914	Remote Similarity	NPD6322	Clinical (unspecified phase)
0.6913	Remote Similarity	NPD2429	Approved
0.6913	Remote Similarity	NPD1421	Approved
0.6913	Remote Similarity	NPD2428	Approved
0.6913	Remote Similarity	NPD1420	Approved
0.6909	Remote Similarity	NPD6876	Approved
0.6909	Remote Similarity	NPD6875	Approved
0.6908	Remote Similarity	NPD2614	Approved
0.6894	Remote Similarity	NPD5295	Discontinued
0.6887	Remote Similarity	NPD7018	Phase 2
0.6879	Remote Similarity	NPD6029	Clinical (unspecified phase)
0.6879	Remote Similarity	NPD6028	Clinical (unspecified phase)
0.6875	Remote Similarity	NPD5481	Discontinued
0.6875	Remote Similarity	NPD2557	Approved
0.6871	Remote Similarity	NPD2556	Approved
0.6871	Remote Similarity	NPD2554	Approved
0.6867	Remote Similarity	NPD196	Phase 1
0.6864	Remote Similarity	NPD2098	Approved
0.6864	Remote Similarity	NPD1309	Phase 2
0.6864	Remote Similarity	NPD1307	Phase 2
0.6859	Remote Similarity	NPD3054	Approved
0.6859	Remote Similarity	NPD3052	Approved
0.6859	Remote Similarity	NPD2492	Phase 1
0.6845	Remote Similarity	NPD7318	Phase 3
0.6829	Remote Similarity	NPD3639	Approved
0.6829	Remote Similarity	NPD1670	Discontinued
0.6829	Remote Similarity	NPD3641	Approved
0.6829	Remote Similarity	NPD3640	Phase 3
0.6818	Remote Similarity	NPD3056	Clinical (unspecified phase)
0.6818	Remote Similarity	NPD6654	Clinical (unspecified phase)
0.6813	Remote Similarity	NPD6364	Approved
0.6813	Remote Similarity	NPD44	Approved
0.681	Remote Similarity	NPD2335	Discontinued
0.6809	Remote Similarity	NPD3802	Phase 3
0.6807	Remote Similarity	NPD2592	Discontinued
0.6803	Remote Similarity	NPD3444	Approved
0.6803	Remote Similarity	NPD3049	Approved
0.6803	Remote Similarity	NPD3443	Approved
0.6803	Remote Similarity	NPD3445	Approved
0.68	Remote Similarity	NPD4503	Phase 2
0.68	Remote Similarity	NPD6582	Phase 2
0.68	Remote Similarity	NPD6542	Approved
0.68	Remote Similarity	NPD6540	Phase 3
0.68	Remote Similarity	NPD6543	Approved
0.68	Remote Similarity	NPD6539	Approved
0.68	Remote Similarity	NPD5313	Approved
0.68	Remote Similarity	NPD6583	Phase 3
0.68	Remote Similarity	NPD5312	Approved
0.6797	Remote Similarity	NPD682	Discontinued
0.6792	Remote Similarity	NPD6800	Clinical (unspecified phase)
0.6792	Remote Similarity	NPD3656	Approved
0.679	Remote Similarity	NPD3281	Clinical (unspecified phase)
0.679	Remote Similarity	NPD6666	Approved
0.679	Remote Similarity	NPD6667	Approved
0.6786	Remote Similarity	NPD5374	Approved
0.6786	Remote Similarity	NPD5294	Clinical (unspecified phase)
0.6786	Remote Similarity	NPD5373	Approved
0.6776	Remote Similarity	NPD2987	Approved
0.6776	Remote Similarity	NPD2990	Approved
0.6774	Remote Similarity	NPD3532	Approved
0.6774	Remote Similarity	NPD3530	Approved
0.6774	Remote Similarity	NPD3531	Approved
0.6772	Remote Similarity	NPD6380	Phase 1
0.6772	Remote Similarity	NPD2164	Clinical (unspecified phase)
0.6772	Remote Similarity	NPD5055	Clinical (unspecified phase)
0.677	Remote Similarity	NPD6748	Discontinued
0.6768	Remote Similarity	NPD2236	Approved
0.6766	Remote Similarity	NPD6385	Approved
0.6766	Remote Similarity	NPD6386	Approved
0.6765	Remote Similarity	NPD6533	Clinical (unspecified phase)
0.676	Remote Similarity	NPD4483	Discontinued
0.6753	Remote Similarity	NPD6039	Approved
0.6752	Remote Similarity	NPD4579	Clinical (unspecified phase)
0.675	Remote Similarity	NPD2897	Discontinued
0.6748	Remote Similarity	NPD3124	Discontinued
0.6747	Remote Similarity	NPD746	Clinical (unspecified phase)
0.6744	Remote Similarity	NPD2017	Approved
0.6744	Remote Similarity	NPD2890	Approved
0.6744	Remote Similarity	NPD2889	Approved
0.6744	Remote Similarity	NPD2888	Approved
0.674	Remote Similarity	NPD7291	Discontinued
0.6737	Remote Similarity	NPD6551	Clinical (unspecified phase)
0.6731	Remote Similarity	NPD3109	Approved
0.6731	Remote Similarity	NPD3110	Approved
0.6726	Remote Similarity	NPD6844	Discontinued
0.6726	Remote Similarity	NPD7248	Discontinued
0.6724	Remote Similarity	NPD3451	Clinical (unspecified phase)
0.6711	Remote Similarity	NPD1820	Approved
0.6711	Remote Similarity	NPD1819	Approved
0.6711	Remote Similarity	NPD1818	Approved
0.6711	Remote Similarity	NPD1817	Approved
0.671	Remote Similarity	NPD7294	Phase 1
0.671	Remote Similarity	NPD6812	Clinical (unspecified phase)
0.6709	Remote Similarity	NPD1536	Approved
0.6707	Remote Similarity	NPD6419	Discontinued
0.6707	Remote Similarity	NPD4739	Approved
0.6705	Remote Similarity	NPD4166	Phase 2

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