NPASS Compound

Structure

NPC134454 OpenBabel07101718242D 24 25 0 0 1 0 0 0 0 0999 V2000 -3.6143 4.7247 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0996 6.3086 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3855 2.2494 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8527 1.2850 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7853 4.1304 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9852 5.0709 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8708 3.8333 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2436 2.5956 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3545 1.7658 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3545 -0.1573 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4213 -0.6328 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8997 5.3681 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6709 2.8927 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1872 0.3235 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 3.1872 1.2850 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 1.5218 1.2850 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6434 0.7146 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 0.4808 -0.8327 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5218 0.3235 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 4.0200 -0.1573 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.6891 1.7658 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.0897 -1.7111 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 4.0200 1.7658 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.0000 -0.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1 12 1 0 0 0 0 2 12 1 0 0 0 0 3 13 1 0 0 0 0 4 23 1 0 0 0 0 5 6 1 0 0 0 0 5 7 1 0 0 0 0 6 12 2 0 0 0 0 7 13 1 0 0 0 0 8 13 2 0 0 0 0 8 17 1 0 0 0 0 9 15 1 0 0 0 0 9 16 1 0 0 0 0 10 14 1 0 0 0 0 11 18 1 0 0 0 0 11 19 1 0 0 0 0 14 15 1 0 0 0 0 14 20 1 1 0 0 0 15 23 1 6 0 0 0 16 19 1 0 0 0 0 16 21 2 0 0 0 0 17 19 1 6 0 0 0 17 24 1 0 0 0 0 18 22 2 0 0 0 0 18 24 1 0 0 0 0 19 10 1 1 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	336.19
Volume:	353.473
LogP:	2.523
LogD:	2.407
LogS:	-4.059
# Rotatable Bonds:	5
TPSA:	72.83
# H-Bond Aceptor:	5
# H-Bond Donor:	1
# Rings:	2
# Heavy Atoms:	5

MedChem Properties

QED Drug-Likeness Score:	0.617
Synthetic Accessibility Score:	4.949
Fsp3:	0.684
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Accepted
GSK Rule:	Accepted
BMS Rule:	0
Golden Triangle Rule:	Accepted
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-4.668
MDCK Permeability:	2.618448888824787e-05
Pgp-inhibitor:	0.977
Pgp-substrate:	0.932
Human Intestinal Absorption (HIA):	0.798
20% Bioavailability (F20%):	0.638
30% Bioavailability (F30%):	0.238

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.974
Plasma Protein Binding (PPB):	88.42830657958984%
Volume Distribution (VD):	1.653
Pgp-substrate:	9.405838012695312%

ADMET: Metabolism

CYP1A2-inhibitor:	0.016
CYP1A2-substrate:	0.096
CYP2C19-inhibitor:	0.057
CYP2C19-substrate:	0.71
CYP2C9-inhibitor:	0.037
CYP2C9-substrate:	0.161
CYP2D6-inhibitor:	0.012
CYP2D6-substrate:	0.097
CYP3A4-inhibitor:	0.219
CYP3A4-substrate:	0.261

ADMET: Excretion

Clearance (CL):	9.203
Half-life (T1/2):	0.826

ADMET: Toxicity

hERG Blockers:	0.016
Human Hepatotoxicity (H-HT):	0.784
Drug-inuced Liver Injury (DILI):	0.181
AMES Toxicity:	0.492
Rat Oral Acute Toxicity:	0.825
Maximum Recommended Daily Dose:	0.15
Skin Sensitization:	0.432
Carcinogencity:	0.097
Eye Corrosion:	0.008
Eye Irritation:	0.025
Respiratory Toxicity:	0.443

Download Data

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

Natural Product: NPC134454

Natural Product ID:	NPC134454
*Common Name:**	(+)-Miliusane Ii
IUPAC Name:	(1R,5R,8S,9S)-1-[(1E)-2,6-dimethylhepta-1,5-dienyl]-9-hydroxy-8-methoxy-2-oxaspiro[4.5]decane-3,6-dione
Synonyms:	(+)-Miliusane II
Standard InCHIKey:	RNXGMPDMYPADJI-UUZSYRILSA-N
Standard InCHI:	InChI=1S/C19H28O5/c1-12(2)6-5-7-13(3)8-17-19(11-18(22)24-17)10-14(20)15(23-4)9-16(19)21/h6,8,14-15,17,20H,5,7,9-11H2,1-4H3/b13-8+/t14-,15-,17+,19-/m0/s1
SMILES:	CO[C@H]1CC(=O)[C@]2(C[C@@H]1O)CC(=O)O[C@@H]2/C=C(/CCC=C(C)C)C
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL425038
PubChem CID:	11652942
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0000050] Lactones [CHEMONTID:0001245] Gamma butyrolactones

*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
NPO22093	Miliusa sinensis	Species	Annonaceae	Eukaryota	dried leaves, twigs, and flowers	Vietnam	n.a.	PMID[16420055]
NPO22093	Miliusa sinensis	Species	Annonaceae	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
IC50	10

Activity Type	# Activity
Cell Line	10

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT91	Cell Line	KB	Homo sapiens	IC50	=	5450.0	nM	PMID[486373]
NPT1034	Cell Line	Lu1	Homo sapiens	IC50	=	5800.0	nM	PMID[486373]
NPT1851	Cell Line	Col2	Homo sapiens	IC50	=	9400.0	nM	PMID[486373]
NPT858	Cell Line	LNCaP	Homo sapiens	IC50	=	19640.0	nM	PMID[486373]
NPT83	Cell Line	MCF7	Homo sapiens	IC50	=	21340.0	nM	PMID[486373]
NPT116	Cell Line	HL-60	Homo sapiens	IC50	=	1730.0	nM	PMID[486373]
NPT737	Cell Line	HUVEC	Homo sapiens	IC50	=	6550.0	nM	PMID[486373]
NPT81	Cell Line	A549	Homo sapiens	IC50	=	18400.0	nM	PMID[486374]
NPT1083	Cell Line	A-375	Homo sapiens	IC50	=	9860.0	nM	PMID[486374]
NPT393	Cell Line	HCT-116	Homo sapiens	IC50	=	17200.0	nM	PMID[486374]

☑ 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 NPC134454 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	180
0.1-0.2	1124
0.2-0.3	4103
0.3-0.4	7444
0.4-0.5	14198
0.5-0.6	7563
0.6-0.7	6388
0.7-0.8	1661
0.8-0.85	29
0.85-0.9	1
0.9-0.95	2
0.95-1	4

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC17326
0.9889	High Similarity	NPC11396
0.9889	High Similarity	NPC21302
0.9444	High Similarity	NPC233437
0.9444	High Similarity	NPC207641
0.8431	Intermediate Similarity	NPC230541
0.8317	Intermediate Similarity	NPC110989
0.8269	Intermediate Similarity	NPC141350
0.8235	Intermediate Similarity	NPC203659
0.8229	Intermediate Similarity	NPC30515
0.8224	Intermediate Similarity	NPC117712
0.8218	Intermediate Similarity	NPC225353
0.8155	Intermediate Similarity	NPC102352
0.8144	Intermediate Similarity	NPC475912
0.8144	Intermediate Similarity	NPC81419
0.8144	Intermediate Similarity	NPC179746
0.8137	Intermediate Similarity	NPC69171
0.8137	Intermediate Similarity	NPC474165
0.8125	Intermediate Similarity	NPC473455
0.8125	Intermediate Similarity	NPC51004
0.8119	Intermediate Similarity	NPC472753
0.8113	Intermediate Similarity	NPC188738
0.8105	Intermediate Similarity	NPC202672
0.8095	Intermediate Similarity	NPC42662
0.8073	Intermediate Similarity	NPC53396
0.8073	Intermediate Similarity	NPC98249
0.8061	Intermediate Similarity	NPC81386
0.8061	Intermediate Similarity	NPC250075
0.8061	Intermediate Similarity	NPC474035
0.8041	Intermediate Similarity	NPC12172
0.8041	Intermediate Similarity	NPC184463
0.8041	Intermediate Similarity	NPC208886
0.8039	Intermediate Similarity	NPC472754
0.8039	Intermediate Similarity	NPC474709
0.8039	Intermediate Similarity	NPC183571
0.8037	Intermediate Similarity	NPC476801
0.8021	Intermediate Similarity	NPC87306
0.8021	Intermediate Similarity	NPC307411
0.8	Intermediate Similarity	NPC473248
0.8	Intermediate Similarity	NPC277017
0.8	Intermediate Similarity	NPC94377
0.8	Intermediate Similarity	NPC154608
0.8	Intermediate Similarity	NPC192813
0.8	Intermediate Similarity	NPC284707
0.7982	Intermediate Similarity	NPC478216
0.798	Intermediate Similarity	NPC270013
0.798	Intermediate Similarity	NPC36954
0.798	Intermediate Similarity	NPC214694
0.798	Intermediate Similarity	NPC14961
0.7963	Intermediate Similarity	NPC478212
0.7961	Intermediate Similarity	NPC4620
0.7961	Intermediate Similarity	NPC475945
0.7961	Intermediate Similarity	NPC475321
0.7961	Intermediate Similarity	NPC474775
0.7961	Intermediate Similarity	NPC472755
0.7961	Intermediate Similarity	NPC475871
0.7959	Intermediate Similarity	NPC212486
0.7959	Intermediate Similarity	NPC476300
0.7944	Intermediate Similarity	NPC100329
0.7944	Intermediate Similarity	NPC97939
0.7944	Intermediate Similarity	NPC247031
0.7944	Intermediate Similarity	NPC132790
0.7938	Intermediate Similarity	NPC476004
0.7938	Intermediate Similarity	NPC474761
0.7928	Intermediate Similarity	NPC470186
0.7925	Intermediate Similarity	NPC478210
0.7909	Intermediate Similarity	NPC469684
0.7909	Intermediate Similarity	NPC476713
0.7909	Intermediate Similarity	NPC476712
0.7909	Intermediate Similarity	NPC478204
0.7909	Intermediate Similarity	NPC58662
0.7905	Intermediate Similarity	NPC144854
0.7905	Intermediate Similarity	NPC3316
0.79	Intermediate Similarity	NPC473859
0.7885	Intermediate Similarity	NPC475676
0.7885	Intermediate Similarity	NPC220964
0.7885	Intermediate Similarity	NPC472756
0.7885	Intermediate Similarity	NPC100487
0.7885	Intermediate Similarity	NPC258532
0.7876	Intermediate Similarity	NPC312833
0.787	Intermediate Similarity	NPC472002
0.787	Intermediate Similarity	NPC269530
0.787	Intermediate Similarity	NPC473877
0.7864	Intermediate Similarity	NPC149371
0.7864	Intermediate Similarity	NPC474747
0.7857	Intermediate Similarity	NPC475003
0.785	Intermediate Similarity	NPC478211
0.785	Intermediate Similarity	NPC46407
0.785	Intermediate Similarity	NPC210005
0.7843	Intermediate Similarity	NPC306856
0.7843	Intermediate Similarity	NPC288876
0.7843	Intermediate Similarity	NPC474718
0.7838	Intermediate Similarity	NPC478205
0.7838	Intermediate Similarity	NPC108581
0.7838	Intermediate Similarity	NPC478206
0.7835	Intermediate Similarity	NPC474032
0.783	Intermediate Similarity	NPC151393
0.783	Intermediate Similarity	NPC19412
0.7822	Intermediate Similarity	NPC474343
0.7822	Intermediate Similarity	NPC40812
0.7818	Intermediate Similarity	NPC476711
0.7818	Intermediate Similarity	NPC207217
0.7818	Intermediate Similarity	NPC476710
0.7812	Intermediate Similarity	NPC179659
0.781	Intermediate Similarity	NPC127609
0.781	Intermediate Similarity	NPC469607
0.7807	Intermediate Similarity	NPC91693
0.7807	Intermediate Similarity	NPC105926
0.7807	Intermediate Similarity	NPC18945
0.7807	Intermediate Similarity	NPC265557
0.78	Intermediate Similarity	NPC475659
0.78	Intermediate Similarity	NPC471142
0.7798	Intermediate Similarity	NPC475966
0.7789	Intermediate Similarity	NPC155873
0.7789	Intermediate Similarity	NPC21469
0.7788	Intermediate Similarity	NPC99266
0.7788	Intermediate Similarity	NPC159533
0.7788	Intermediate Similarity	NPC470779
0.7788	Intermediate Similarity	NPC472747
0.7788	Intermediate Similarity	NPC472750
0.7778	Intermediate Similarity	NPC469645
0.7778	Intermediate Similarity	NPC162205
0.7778	Intermediate Similarity	NPC469692
0.7778	Intermediate Similarity	NPC273579
0.7778	Intermediate Similarity	NPC469656
0.7778	Intermediate Similarity	NPC295204
0.7778	Intermediate Similarity	NPC474846
0.7778	Intermediate Similarity	NPC469655
0.7778	Intermediate Similarity	NPC317107
0.7778	Intermediate Similarity	NPC288240
0.7767	Intermediate Similarity	NPC128733
0.7767	Intermediate Similarity	NPC474742
0.7767	Intermediate Similarity	NPC185141
0.7767	Intermediate Similarity	NPC308824
0.7767	Intermediate Similarity	NPC110443
0.7767	Intermediate Similarity	NPC133907
0.7767	Intermediate Similarity	NPC47880
0.7767	Intermediate Similarity	NPC46998
0.7766	Intermediate Similarity	NPC52923
0.7757	Intermediate Similarity	NPC273433
0.7757	Intermediate Similarity	NPC472534
0.7757	Intermediate Similarity	NPC475922
0.7757	Intermediate Similarity	NPC143706
0.7757	Intermediate Similarity	NPC153239
0.7755	Intermediate Similarity	NPC473619
0.7755	Intermediate Similarity	NPC158488
0.7755	Intermediate Similarity	NPC232202
0.7748	Intermediate Similarity	NPC296822
0.7748	Intermediate Similarity	NPC473590
0.7748	Intermediate Similarity	NPC176513
0.7748	Intermediate Similarity	NPC470775
0.7745	Intermediate Similarity	NPC187761
0.7745	Intermediate Similarity	NPC23364
0.7745	Intermediate Similarity	NPC471932
0.7745	Intermediate Similarity	NPC83895
0.7745	Intermediate Similarity	NPC471144
0.7739	Intermediate Similarity	NPC24651
0.7739	Intermediate Similarity	NPC476729
0.7736	Intermediate Similarity	NPC194620
0.7736	Intermediate Similarity	NPC72813
0.7736	Intermediate Similarity	NPC474421
0.7736	Intermediate Similarity	NPC324327
0.7736	Intermediate Similarity	NPC326994
0.7736	Intermediate Similarity	NPC112780
0.7732	Intermediate Similarity	NPC153570
0.7732	Intermediate Similarity	NPC153805
0.7727	Intermediate Similarity	NPC73314
0.7723	Intermediate Similarity	NPC477921
0.7723	Intermediate Similarity	NPC476315
0.7723	Intermediate Similarity	NPC256227
0.7719	Intermediate Similarity	NPC269642
0.7714	Intermediate Similarity	NPC472748
0.7714	Intermediate Similarity	NPC146731
0.7714	Intermediate Similarity	NPC474741
0.7714	Intermediate Similarity	NPC296950
0.7708	Intermediate Similarity	NPC478112
0.7706	Intermediate Similarity	NPC317687
0.77	Intermediate Similarity	NPC121825
0.7692	Intermediate Similarity	NPC469606
0.7692	Intermediate Similarity	NPC137430
0.7692	Intermediate Similarity	NPC273005
0.7692	Intermediate Similarity	NPC31058
0.7692	Intermediate Similarity	NPC295791
0.7692	Intermediate Similarity	NPC478156
0.7685	Intermediate Similarity	NPC478209
0.7685	Intermediate Similarity	NPC161816
0.7685	Intermediate Similarity	NPC115257
0.7685	Intermediate Similarity	NPC5103
0.7684	Intermediate Similarity	NPC38569
0.7684	Intermediate Similarity	NPC163615
0.7679	Intermediate Similarity	NPC470776
0.7679	Intermediate Similarity	NPC106644
0.7677	Intermediate Similarity	NPC475972
0.7677	Intermediate Similarity	NPC230623
0.7677	Intermediate Similarity	NPC473321
0.767	Intermediate Similarity	NPC117685
0.7664	Intermediate Similarity	NPC233379
0.7664	Intermediate Similarity	NPC476802
0.7664	Intermediate Similarity	NPC14862
0.7664	Intermediate Similarity	NPC37628

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 NPC134454 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	149
0.1-0.2	1577
0.2-0.3	3720
0.3-0.4	2379
0.4-0.5	811
0.5-0.6	324
0.6-0.7	176
0.7-0.8	14
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
0.7573	Intermediate Similarity	NPD4225	Approved
0.75	Intermediate Similarity	NPD5345	Clinical (unspecified phase)
0.75	Intermediate Similarity	NPD7983	Approved
0.7451	Intermediate Similarity	NPD1698	Clinical (unspecified phase)
0.74	Intermediate Similarity	NPD46	Approved
0.74	Intermediate Similarity	NPD6698	Approved
0.7364	Intermediate Similarity	NPD6371	Approved
0.7182	Intermediate Similarity	NPD6686	Approved
0.7117	Intermediate Similarity	NPD4061	Clinical (unspecified phase)
0.7091	Intermediate Similarity	NPD7899	Clinical (unspecified phase)
0.7087	Intermediate Similarity	NPD5778	Approved
0.7087	Intermediate Similarity	NPD5779	Approved
0.7075	Intermediate Similarity	NPD7638	Approved
0.7054	Intermediate Similarity	NPD5955	Clinical (unspecified phase)
0.7034	Intermediate Similarity	NPD8515	Approved
0.7034	Intermediate Similarity	NPD8513	Phase 3
0.7034	Intermediate Similarity	NPD8517	Approved
0.7034	Intermediate Similarity	NPD8516	Approved
0.7009	Intermediate Similarity	NPD7639	Approved
0.7009	Intermediate Similarity	NPD7640	Approved
0.7	Intermediate Similarity	NPD5786	Approved
0.6983	Remote Similarity	NPD7115	Discovery
0.6949	Remote Similarity	NPD6319	Approved
0.6923	Remote Similarity	NPD6399	Phase 3
0.6911	Remote Similarity	NPD7319	Approved
0.69	Remote Similarity	NPD1733	Clinical (unspecified phase)
0.69	Remote Similarity	NPD1694	Approved
0.6893	Remote Similarity	NPD5785	Approved
0.687	Remote Similarity	NPD4632	Approved
0.6857	Remote Similarity	NPD5282	Discontinued
0.6842	Remote Similarity	NPD8413	Clinical (unspecified phase)
0.6827	Remote Similarity	NPD6411	Approved
0.6814	Remote Similarity	NPD8132	Clinical (unspecified phase)
0.6803	Remote Similarity	NPD7507	Approved
0.6789	Remote Similarity	NPD5344	Discontinued
0.6786	Remote Similarity	NPD5954	Clinical (unspecified phase)
0.6777	Remote Similarity	NPD8328	Phase 3
0.675	Remote Similarity	NPD6921	Approved
0.6748	Remote Similarity	NPD8074	Phase 3
0.6731	Remote Similarity	NPD7838	Discovery
0.6721	Remote Similarity	NPD7492	Approved
0.6696	Remote Similarity	NPD6008	Approved
0.6667	Remote Similarity	NPD6372	Approved
0.6667	Remote Similarity	NPD6616	Approved
0.6667	Remote Similarity	NPD7902	Approved
0.6667	Remote Similarity	NPD6373	Approved
0.6667	Remote Similarity	NPD6059	Approved
0.6667	Remote Similarity	NPD6054	Approved
0.6635	Remote Similarity	NPD5764	Clinical (unspecified phase)
0.6635	Remote Similarity	NPD6101	Approved
0.6613	Remote Similarity	NPD7078	Approved
0.6613	Remote Similarity	NPD8293	Discontinued
0.6612	Remote Similarity	NPD6015	Approved
0.6612	Remote Similarity	NPD6016	Approved
0.6606	Remote Similarity	NPD8029	Clinical (unspecified phase)
0.66	Remote Similarity	NPD4752	Clinical (unspecified phase)
0.66	Remote Similarity	NPD4269	Approved
0.66	Remote Similarity	NPD6435	Approved
0.66	Remote Similarity	NPD4270	Approved
0.6574	Remote Similarity	NPD7839	Suspended
0.656	Remote Similarity	NPD7736	Approved
0.6557	Remote Similarity	NPD5988	Approved
0.6557	Remote Similarity	NPD6370	Approved
0.6555	Remote Similarity	NPD6009	Approved
0.6555	Remote Similarity	NPD8295	Clinical (unspecified phase)
0.6552	Remote Similarity	NPD6649	Approved
0.6552	Remote Similarity	NPD6650	Approved
0.6549	Remote Similarity	NPD5739	Approved
0.6549	Remote Similarity	NPD6675	Approved
0.6549	Remote Similarity	NPD6402	Approved
0.6549	Remote Similarity	NPD7128	Approved
0.6531	Remote Similarity	NPD5784	Clinical (unspecified phase)
0.6509	Remote Similarity	NPD7637	Suspended
0.65	Remote Similarity	NPD5369	Approved
0.6496	Remote Similarity	NPD8297	Approved
0.6491	Remote Similarity	NPD6412	Phase 2
0.6491	Remote Similarity	NPD5697	Approved
0.6491	Remote Similarity	NPD5701	Approved
0.6475	Remote Similarity	NPD5983	Phase 2
0.6466	Remote Similarity	NPD4634	Approved
0.6462	Remote Similarity	NPD8387	Clinical (unspecified phase)
0.6441	Remote Similarity	NPD8133	Approved
0.6435	Remote Similarity	NPD6899	Approved
0.6435	Remote Similarity	NPD6011	Approved
0.6435	Remote Similarity	NPD7320	Approved
0.6435	Remote Similarity	NPD6881	Approved
0.6429	Remote Similarity	NPD7632	Discontinued
0.6422	Remote Similarity	NPD4697	Phase 3
0.6412	Remote Similarity	NPD7966	Clinical (unspecified phase)
0.6408	Remote Similarity	NPD5363	Approved
0.6408	Remote Similarity	NPD6082	Clinical (unspecified phase)
0.64	Remote Similarity	NPD4252	Approved
0.64	Remote Similarity	NPD5368	Approved
0.6396	Remote Similarity	NPD6648	Approved
0.6392	Remote Similarity	NPD8039	Approved
0.6389	Remote Similarity	NPD7748	Approved
0.6389	Remote Similarity	NPD7901	Clinical (unspecified phase)
0.6389	Remote Similarity	NPD7900	Approved
0.6385	Remote Similarity	NPD8415	Approved
0.6379	Remote Similarity	NPD6014	Approved
0.6379	Remote Similarity	NPD6012	Approved
0.6379	Remote Similarity	NPD6013	Approved
0.6373	Remote Similarity	NPD6110	Phase 1
0.6373	Remote Similarity	NPD7154	Phase 3
0.6371	Remote Similarity	NPD7604	Phase 2
0.6356	Remote Similarity	NPD6053	Discontinued
0.6355	Remote Similarity	NPD7515	Phase 2
0.6355	Remote Similarity	NPD8034	Phase 2
0.6355	Remote Similarity	NPD8035	Phase 2
0.6346	Remote Similarity	NPD3618	Phase 1
0.6346	Remote Similarity	NPD4249	Approved
0.6341	Remote Similarity	NPD8444	Approved
0.6325	Remote Similarity	NPD7290	Approved
0.6325	Remote Similarity	NPD7102	Approved
0.6325	Remote Similarity	NPD6883	Approved
0.6321	Remote Similarity	NPD5328	Approved
0.6321	Remote Similarity	NPD1695	Approved
0.6311	Remote Similarity	NPD7516	Approved
0.6299	Remote Similarity	NPD6033	Approved
0.6286	Remote Similarity	NPD4251	Approved
0.6286	Remote Similarity	NPD4250	Approved
0.6275	Remote Similarity	NPD5209	Approved
0.6275	Remote Similarity	NPD3667	Approved
0.6271	Remote Similarity	NPD6401	Clinical (unspecified phase)
0.6271	Remote Similarity	NPD6847	Approved
0.6271	Remote Similarity	NPD6617	Approved
0.6271	Remote Similarity	NPD6869	Approved
0.6271	Remote Similarity	NPD8130	Phase 1
0.627	Remote Similarity	NPD8451	Approved
0.627	Remote Similarity	NPD6336	Discontinued
0.624	Remote Similarity	NPD7642	Approved
0.623	Remote Similarity	NPD7327	Approved
0.623	Remote Similarity	NPD7328	Approved
0.622	Remote Similarity	NPD8448	Approved
0.6218	Remote Similarity	NPD6882	Approved
0.6216	Remote Similarity	NPD4755	Approved
0.6214	Remote Similarity	NPD5362	Discontinued
0.6204	Remote Similarity	NPD6079	Approved
0.6204	Remote Similarity	NPD4810	Clinical (unspecified phase)
0.6154	Remote Similarity	NPD7260	Phase 2
0.6154	Remote Similarity	NPD4786	Approved
0.614	Remote Similarity	NPD5211	Phase 2
0.6132	Remote Similarity	NPD7524	Approved
0.6129	Remote Similarity	NPD8377	Approved
0.6129	Remote Similarity	NPD8294	Approved
0.6126	Remote Similarity	NPD5221	Approved
0.6126	Remote Similarity	NPD5222	Approved
0.6126	Remote Similarity	NPD5220	Clinical (unspecified phase)
0.6117	Remote Similarity	NPD4800	Clinical (unspecified phase)
0.6111	Remote Similarity	NPD7830	Approved
0.6111	Remote Similarity	NPD7829	Approved
0.6106	Remote Similarity	NPD5286	Approved
0.6106	Remote Similarity	NPD4700	Approved
0.6106	Remote Similarity	NPD5285	Approved
0.6106	Remote Similarity	NPD4696	Approved
0.608	Remote Similarity	NPD8335	Approved
0.608	Remote Similarity	NPD8378	Approved
0.608	Remote Similarity	NPD8379	Approved
0.608	Remote Similarity	NPD8296	Approved
0.608	Remote Similarity	NPD8380	Approved
0.608	Remote Similarity	NPD8033	Approved
0.608	Remote Similarity	NPD6291	Clinical (unspecified phase)
0.6078	Remote Similarity	NPD5790	Clinical (unspecified phase)
0.6077	Remote Similarity	NPD8391	Approved
0.6077	Remote Similarity	NPD8390	Approved
0.6077	Remote Similarity	NPD8392	Approved
0.6071	Remote Similarity	NPD6084	Phase 2
0.6071	Remote Similarity	NPD6083	Phase 2
0.6071	Remote Similarity	NPD5173	Approved
0.6066	Remote Similarity	NPD6274	Approved
0.6063	Remote Similarity	NPD8340	Approved
0.6063	Remote Similarity	NPD8342	Approved
0.6063	Remote Similarity	NPD8299	Approved
0.6063	Remote Similarity	NPD8341	Approved
0.6053	Remote Similarity	NPD5223	Approved
0.6053	Remote Similarity	NPD1700	Approved
0.6038	Remote Similarity	NPD6684	Approved
0.6038	Remote Similarity	NPD7521	Approved
0.6038	Remote Similarity	NPD5330	Approved
0.6038	Remote Similarity	NPD6409	Approved
0.6038	Remote Similarity	NPD7334	Approved
0.6038	Remote Similarity	NPD7146	Approved
0.6036	Remote Similarity	NPD5695	Phase 3
0.6034	Remote Similarity	NPD5141	Approved
0.6019	Remote Similarity	NPD5370	Suspended
0.6018	Remote Similarity	NPD5696	Approved
0.6016	Remote Similarity	NPD6317	Approved
0.6016	Remote Similarity	NPD8273	Phase 1
0.6	Remote Similarity	NPD5226	Approved
0.6	Remote Similarity	NPD6400	Clinical (unspecified phase)
0.6	Remote Similarity	NPD4202	Approved
0.6	Remote Similarity	NPD4633	Approved
0.6	Remote Similarity	NPD5225	Approved
0.6	Remote Similarity	NPD3666	Approved
0.6	Remote Similarity	NPD3133	Approved
0.6	Remote Similarity	NPD5224	Approved
0.6	Remote Similarity	NPD3665	Phase 1
0.5985	Remote Similarity	NPD6845	Suspended
0.5984	Remote Similarity	NPD6067	Discontinued
0.5983	Remote Similarity	NPD5048	Discontinued

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