NPASS Compound

Structure

NPC11396 OpenBabel07101718182D 23 24 0 0 1 0 0 0 0 0999 V2000 0.1582 6.9899 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2708 5.7542 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3833 2.2458 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1560 4.4695 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3556 5.4085 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8694 3.8271 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2432 2.5915 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3508 1.7630 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3508 -0.1570 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4190 -0.6318 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3578 6.0509 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6698 2.8881 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1821 1.2830 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 3.1821 0.3230 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 1.5194 1.2830 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6424 0.7134 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 0.4800 -0.8314 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5194 0.3230 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 4.0135 1.7630 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 4.0135 -0.1570 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.6880 1.7630 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.0895 -1.7084 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 11 1 0 0 0 0 2 11 1 0 0 0 0 3 12 1 0 0 0 0 4 5 1 0 0 0 0 4 6 1 0 0 0 0 5 11 2 0 0 0 0 6 12 1 0 0 0 0 7 12 2 0 0 0 0 7 16 1 0 0 0 0 8 13 1 0 0 0 0 8 15 1 0 0 0 0 9 14 1 0 0 0 0 10 17 1 0 0 0 0 10 18 1 0 0 0 0 13 14 1 0 0 0 0 13 19 1 6 0 0 0 14 20 1 1 0 0 0 15 18 1 0 0 0 0 15 21 2 0 0 0 0 16 18 1 6 0 0 0 16 23 1 0 0 0 0 17 22 2 0 0 0 0 17 23 1 0 0 0 0 18 9 1 1 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	322.18
Volume:	336.177
LogP:	2.264
LogD:	2.011
LogS:	-3.856
# Rotatable Bonds:	4
TPSA:	83.83
# H-Bond Aceptor:	5
# H-Bond Donor:	2
# Rings:	2
# Heavy Atoms:	5

MedChem Properties

QED Drug-Likeness Score:	0.611
Synthetic Accessibility Score:	4.915
Fsp3:	0.667
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:	-4.782
MDCK Permeability:	3.656523767858744e-05
Pgp-inhibitor:	0.804
Pgp-substrate:	0.98
Human Intestinal Absorption (HIA):	0.89
20% Bioavailability (F20%):	0.697
30% Bioavailability (F30%):	0.042

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.964
Plasma Protein Binding (PPB):	87.20922088623047%
Volume Distribution (VD):	1.216
Pgp-substrate:	11.450277328491211%

ADMET: Metabolism

CYP1A2-inhibitor:	0.021
CYP1A2-substrate:	0.096
CYP2C19-inhibitor:	0.067
CYP2C19-substrate:	0.603
CYP2C9-inhibitor:	0.026
CYP2C9-substrate:	0.844
CYP2D6-inhibitor:	0.008
CYP2D6-substrate:	0.087
CYP3A4-inhibitor:	0.121
CYP3A4-substrate:	0.183

ADMET: Excretion

Clearance (CL):	8.728
Half-life (T1/2):	0.888

ADMET: Toxicity

hERG Blockers:	0.014
Human Hepatotoxicity (H-HT):	0.704
Drug-inuced Liver Injury (DILI):	0.067
AMES Toxicity:	0.293
Rat Oral Acute Toxicity:	0.83
Maximum Recommended Daily Dose:	0.208
Skin Sensitization:	0.376
Carcinogencity:	0.114
Eye Corrosion:	0.006
Eye Irritation:	0.023
Respiratory Toxicity:	0.325

Download Data

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

Natural Product: NPC11396

Natural Product ID:	NPC11396
*Common Name:**	(+)-Miliusane Iv
IUPAC Name:	(1R,5R,8S,9S)-1-[(1E)-2,6-dimethylhepta-1,5-dienyl]-8,9-dihydroxy-2-oxaspiro[4.5]decane-3,6-dione
Synonyms:	(+)-Miliusane IV
Standard InCHIKey:	UPYNJRPEKOAWTJ-IIDOJOHISA-N
Standard InCHI:	InChI=1S/C18H26O5/c1-11(2)5-4-6-12(3)7-16-18(10-17(22)23-16)9-14(20)13(19)8-15(18)21/h5,7,13-14,16,19-20H,4,6,8-10H2,1-3H3/b12-7+/t13-,14-,16+,18-/m0/s1
SMILES:	CC(=CCC/C(=C/[C@@H]1[C@@]2(C[C@@H]([C@H](CC2=O)O)O)CC(=O)O1)/C)C
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL383650
PubChem CID:	11638372
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	6

Activity Type	# Activity
Cell Line	6

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT91	Cell Line	KB	Homo sapiens	IC50	=	32170.0	nM	PMID[526250]
NPT1034	Cell Line	Lu1	Homo sapiens	IC50	=	60430.0	nM	PMID[526250]
NPT1851	Cell Line	Col2	Homo sapiens	IC50	=	38450.0	nM	PMID[526250]
NPT858	Cell Line	LNCaP	Homo sapiens	IC50	>	62000.0	nM	PMID[526250]
NPT83	Cell Line	MCF7	Homo sapiens	IC50	=	15780.0	nM	PMID[526250]
NPT116	Cell Line	HL-60	Homo sapiens	IC50	=	18660.0	nM	PMID[526250]

☑ 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 NPC11396 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	176
0.1-0.2	1128
0.2-0.3	4084
0.3-0.4	7573
0.4-0.5	14309
0.5-0.6	7341
0.6-0.7	6390
0.7-0.8	1669
0.8-0.85	21
0.85-0.9	0
0.9-0.95	2
0.95-1	4

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC21302
0.9889	High Similarity	NPC134454
0.9889	High Similarity	NPC17326
0.9333	High Similarity	NPC207641
0.9333	High Similarity	NPC233437
0.8333	Intermediate Similarity	NPC230541
0.8218	Intermediate Similarity	NPC110989
0.8211	Intermediate Similarity	NPC473455
0.8191	Intermediate Similarity	NPC202672
0.8173	Intermediate Similarity	NPC141350
0.8144	Intermediate Similarity	NPC250075
0.8137	Intermediate Similarity	NPC203659
0.8131	Intermediate Similarity	NPC117712
0.8125	Intermediate Similarity	NPC30515
0.8119	Intermediate Similarity	NPC474709
0.8119	Intermediate Similarity	NPC225353
0.8105	Intermediate Similarity	NPC87306
0.8085	Intermediate Similarity	NPC473248
0.8061	Intermediate Similarity	NPC214694
0.8058	Intermediate Similarity	NPC102352
0.8041	Intermediate Similarity	NPC81419
0.8041	Intermediate Similarity	NPC475912
0.8041	Intermediate Similarity	NPC179746
0.8039	Intermediate Similarity	NPC69171
0.8039	Intermediate Similarity	NPC474165
0.8039	Intermediate Similarity	NPC474775
0.8037	Intermediate Similarity	NPC478212
0.8021	Intermediate Similarity	NPC51004
0.802	Intermediate Similarity	NPC472753
0.8019	Intermediate Similarity	NPC188738
0.8	Intermediate Similarity	NPC42662
0.8	Intermediate Similarity	NPC478210
0.7982	Intermediate Similarity	NPC98249
0.7982	Intermediate Similarity	NPC53396
0.7959	Intermediate Similarity	NPC474035
0.7959	Intermediate Similarity	NPC81386
0.7944	Intermediate Similarity	NPC476801
0.7941	Intermediate Similarity	NPC183571
0.7941	Intermediate Similarity	NPC472754
0.7938	Intermediate Similarity	NPC12172
0.7938	Intermediate Similarity	NPC184463
0.7938	Intermediate Similarity	NPC208886
0.7921	Intermediate Similarity	NPC306856
0.7921	Intermediate Similarity	NPC474718
0.7917	Intermediate Similarity	NPC307411
0.7909	Intermediate Similarity	NPC284707
0.7905	Intermediate Similarity	NPC154608
0.7905	Intermediate Similarity	NPC192813
0.7905	Intermediate Similarity	NPC94377
0.7905	Intermediate Similarity	NPC277017
0.79	Intermediate Similarity	NPC474343
0.789	Intermediate Similarity	NPC478216
0.7885	Intermediate Similarity	NPC469607
0.7879	Intermediate Similarity	NPC36954
0.7879	Intermediate Similarity	NPC270013
0.7879	Intermediate Similarity	NPC14961
0.7872	Intermediate Similarity	NPC155873
0.7864	Intermediate Similarity	NPC475945
0.7864	Intermediate Similarity	NPC475321
0.7864	Intermediate Similarity	NPC472755
0.7864	Intermediate Similarity	NPC475871
0.7864	Intermediate Similarity	NPC4620
0.7857	Intermediate Similarity	NPC476300
0.7857	Intermediate Similarity	NPC212486
0.785	Intermediate Similarity	NPC247031
0.785	Intermediate Similarity	NPC100329
0.785	Intermediate Similarity	NPC132790
0.785	Intermediate Similarity	NPC97939
0.7849	Intermediate Similarity	NPC52923
0.7843	Intermediate Similarity	NPC308824
0.7838	Intermediate Similarity	NPC470186
0.7835	Intermediate Similarity	NPC476004
0.7835	Intermediate Similarity	NPC158488
0.7835	Intermediate Similarity	NPC474761
0.7835	Intermediate Similarity	NPC232202
0.7822	Intermediate Similarity	NPC23364
0.7818	Intermediate Similarity	NPC469684
0.7818	Intermediate Similarity	NPC476712
0.7818	Intermediate Similarity	NPC478204
0.7818	Intermediate Similarity	NPC58662
0.7818	Intermediate Similarity	NPC476713
0.7812	Intermediate Similarity	NPC153570
0.781	Intermediate Similarity	NPC3316
0.781	Intermediate Similarity	NPC144854
0.78	Intermediate Similarity	NPC473859
0.7788	Intermediate Similarity	NPC100487
0.7788	Intermediate Similarity	NPC312833
0.7788	Intermediate Similarity	NPC475676
0.7788	Intermediate Similarity	NPC258532
0.7788	Intermediate Similarity	NPC472756
0.7788	Intermediate Similarity	NPC220964
0.7778	Intermediate Similarity	NPC269530
0.7778	Intermediate Similarity	NPC473877
0.7778	Intermediate Similarity	NPC472002
0.7768	Intermediate Similarity	NPC475003
0.7767	Intermediate Similarity	NPC478156
0.7767	Intermediate Similarity	NPC474747
0.7767	Intermediate Similarity	NPC149371
0.7767	Intermediate Similarity	NPC31058
0.7767	Intermediate Similarity	NPC469606
0.7767	Intermediate Similarity	NPC273005
0.7766	Intermediate Similarity	NPC163615
0.7766	Intermediate Similarity	NPC38569
0.7757	Intermediate Similarity	NPC478211
0.7757	Intermediate Similarity	NPC46407
0.7757	Intermediate Similarity	NPC478209
0.7757	Intermediate Similarity	NPC210005
0.7755	Intermediate Similarity	NPC475972
0.7748	Intermediate Similarity	NPC478205
0.7748	Intermediate Similarity	NPC108581
0.7748	Intermediate Similarity	NPC478206
0.7745	Intermediate Similarity	NPC288876
0.7745	Intermediate Similarity	NPC117685
0.7736	Intermediate Similarity	NPC151393
0.7736	Intermediate Similarity	NPC19412
0.7736	Intermediate Similarity	NPC476802
0.7736	Intermediate Similarity	NPC189075
0.7736	Intermediate Similarity	NPC275539
0.7736	Intermediate Similarity	NPC89171
0.7732	Intermediate Similarity	NPC295312
0.7732	Intermediate Similarity	NPC78008
0.7732	Intermediate Similarity	NPC474032
0.7727	Intermediate Similarity	NPC476711
0.7727	Intermediate Similarity	NPC476710
0.7727	Intermediate Similarity	NPC207217
0.7723	Intermediate Similarity	NPC70145
0.7723	Intermediate Similarity	NPC40812
0.7723	Intermediate Similarity	NPC91695
0.7719	Intermediate Similarity	NPC105926
0.7719	Intermediate Similarity	NPC18945
0.7719	Intermediate Similarity	NPC91693
0.7719	Intermediate Similarity	NPC265557
0.7714	Intermediate Similarity	NPC478208
0.7714	Intermediate Similarity	NPC127609
0.7708	Intermediate Similarity	NPC179659
0.7706	Intermediate Similarity	NPC312017
0.7706	Intermediate Similarity	NPC9848
0.7706	Intermediate Similarity	NPC475966
0.77	Intermediate Similarity	NPC475659
0.77	Intermediate Similarity	NPC471142
0.7699	Intermediate Similarity	NPC470779
0.7692	Intermediate Similarity	NPC99266
0.7692	Intermediate Similarity	NPC472747
0.7692	Intermediate Similarity	NPC472750
0.7692	Intermediate Similarity	NPC159533
0.7692	Intermediate Similarity	NPC156681
0.7685	Intermediate Similarity	NPC469656
0.7685	Intermediate Similarity	NPC469655
0.7685	Intermediate Similarity	NPC474846
0.7685	Intermediate Similarity	NPC317107
0.7684	Intermediate Similarity	NPC137033
0.7684	Intermediate Similarity	NPC21469
0.7677	Intermediate Similarity	NPC199543
0.7677	Intermediate Similarity	NPC288240
0.7677	Intermediate Similarity	NPC469692
0.7677	Intermediate Similarity	NPC273579
0.7677	Intermediate Similarity	NPC295204
0.7677	Intermediate Similarity	NPC162205
0.7677	Intermediate Similarity	NPC469645
0.767	Intermediate Similarity	NPC471412
0.767	Intermediate Similarity	NPC110443
0.767	Intermediate Similarity	NPC185141
0.767	Intermediate Similarity	NPC128733
0.767	Intermediate Similarity	NPC47880
0.767	Intermediate Similarity	NPC171759
0.767	Intermediate Similarity	NPC46998
0.767	Intermediate Similarity	NPC474742
0.767	Intermediate Similarity	NPC133907
0.7664	Intermediate Similarity	NPC153239
0.7664	Intermediate Similarity	NPC143706
0.7664	Intermediate Similarity	NPC474243
0.7664	Intermediate Similarity	NPC273433
0.7664	Intermediate Similarity	NPC472534
0.7664	Intermediate Similarity	NPC475922
0.766	Intermediate Similarity	NPC11620
0.7658	Intermediate Similarity	NPC470775
0.7658	Intermediate Similarity	NPC147707
0.7658	Intermediate Similarity	NPC473590
0.7658	Intermediate Similarity	NPC296822
0.7658	Intermediate Similarity	NPC176513
0.7653	Intermediate Similarity	NPC71533
0.7653	Intermediate Similarity	NPC473619
0.7653	Intermediate Similarity	NPC106510
0.7653	Intermediate Similarity	NPC316228
0.7652	Intermediate Similarity	NPC476729
0.7652	Intermediate Similarity	NPC24651
0.7647	Intermediate Similarity	NPC471932
0.7647	Intermediate Similarity	NPC83895
0.7647	Intermediate Similarity	NPC187761
0.7647	Intermediate Similarity	NPC471144
0.7647	Intermediate Similarity	NPC141191
0.7647	Intermediate Similarity	NPC216478
0.7642	Intermediate Similarity	NPC326994
0.7642	Intermediate Similarity	NPC474421
0.7642	Intermediate Similarity	NPC324327
0.7642	Intermediate Similarity	NPC194620
0.7642	Intermediate Similarity	NPC112780
0.7642	Intermediate Similarity	NPC284732
0.7642	Intermediate Similarity	NPC78966
0.7642	Intermediate Similarity	NPC110496

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 NPC11396 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	146
0.1-0.2	1560
0.2-0.3	3712
0.3-0.4	2392
0.4-0.5	827
0.5-0.6	317
0.6-0.7	183
0.7-0.8	13
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.7525	Intermediate Similarity	NPD1698	Clinical (unspecified phase)
0.7476	Intermediate Similarity	NPD4225	Approved
0.7407	Intermediate Similarity	NPD5345	Clinical (unspecified phase)
0.74	Intermediate Similarity	NPD7983	Approved
0.73	Intermediate Similarity	NPD46	Approved
0.73	Intermediate Similarity	NPD6698	Approved
0.7273	Intermediate Similarity	NPD6371	Approved
0.7157	Intermediate Similarity	NPD5779	Approved
0.7157	Intermediate Similarity	NPD5778	Approved
0.7143	Intermediate Similarity	NPD7638	Approved
0.7091	Intermediate Similarity	NPD6686	Approved
0.7075	Intermediate Similarity	NPD7639	Approved
0.7075	Intermediate Similarity	NPD7640	Approved
0.7071	Intermediate Similarity	NPD5786	Approved
0.7027	Intermediate Similarity	NPD4061	Clinical (unspecified phase)
0.7	Intermediate Similarity	NPD7899	Clinical (unspecified phase)
0.699	Remote Similarity	NPD6399	Phase 3
0.697	Remote Similarity	NPD1694	Approved
0.6964	Remote Similarity	NPD5955	Clinical (unspecified phase)
0.6961	Remote Similarity	NPD5785	Approved
0.6949	Remote Similarity	NPD8513	Phase 3
0.6949	Remote Similarity	NPD8515	Approved
0.6949	Remote Similarity	NPD8517	Approved
0.6949	Remote Similarity	NPD8516	Approved
0.6923	Remote Similarity	NPD5282	Discontinued
0.6897	Remote Similarity	NPD7115	Discovery
0.6893	Remote Similarity	NPD6411	Approved
0.6864	Remote Similarity	NPD6319	Approved
0.6829	Remote Similarity	NPD7319	Approved
0.68	Remote Similarity	NPD1733	Clinical (unspecified phase)
0.6783	Remote Similarity	NPD4632	Approved
0.6757	Remote Similarity	NPD6008	Approved
0.6754	Remote Similarity	NPD8413	Clinical (unspecified phase)
0.6729	Remote Similarity	NPD7902	Approved
0.6726	Remote Similarity	NPD6373	Approved
0.6726	Remote Similarity	NPD6372	Approved
0.6726	Remote Similarity	NPD8132	Clinical (unspecified phase)
0.6721	Remote Similarity	NPD7507	Approved
0.6699	Remote Similarity	NPD6101	Approved
0.6699	Remote Similarity	NPD5764	Clinical (unspecified phase)
0.6697	Remote Similarity	NPD5344	Discontinued
0.6696	Remote Similarity	NPD5954	Clinical (unspecified phase)
0.6694	Remote Similarity	NPD8328	Phase 3
0.6667	Remote Similarity	NPD6435	Approved
0.6667	Remote Similarity	NPD4752	Clinical (unspecified phase)
0.6667	Remote Similarity	NPD8074	Phase 3
0.6667	Remote Similarity	NPD6921	Approved
0.6667	Remote Similarity	NPD4270	Approved
0.6667	Remote Similarity	NPD4269	Approved
0.6639	Remote Similarity	NPD7492	Approved
0.6636	Remote Similarity	NPD7839	Suspended
0.6635	Remote Similarity	NPD7838	Discovery
0.6609	Remote Similarity	NPD6650	Approved
0.6609	Remote Similarity	NPD6649	Approved
0.6607	Remote Similarity	NPD5739	Approved
0.6607	Remote Similarity	NPD6402	Approved
0.6607	Remote Similarity	NPD6675	Approved
0.6607	Remote Similarity	NPD7128	Approved
0.6598	Remote Similarity	NPD5784	Clinical (unspecified phase)
0.6585	Remote Similarity	NPD6616	Approved
0.6583	Remote Similarity	NPD6059	Approved
0.6583	Remote Similarity	NPD6054	Approved
0.6571	Remote Similarity	NPD7637	Suspended
0.6566	Remote Similarity	NPD5369	Approved
0.6549	Remote Similarity	NPD5701	Approved
0.6549	Remote Similarity	NPD5697	Approved
0.6532	Remote Similarity	NPD8293	Discontinued
0.6532	Remote Similarity	NPD7078	Approved
0.6529	Remote Similarity	NPD6016	Approved
0.6529	Remote Similarity	NPD6015	Approved
0.6522	Remote Similarity	NPD4634	Approved
0.6514	Remote Similarity	NPD8029	Clinical (unspecified phase)
0.6491	Remote Similarity	NPD6899	Approved
0.6491	Remote Similarity	NPD6881	Approved
0.6491	Remote Similarity	NPD7320	Approved
0.6491	Remote Similarity	NPD6011	Approved
0.6486	Remote Similarity	NPD7632	Discontinued
0.6481	Remote Similarity	NPD4697	Phase 3
0.648	Remote Similarity	NPD7736	Approved
0.6475	Remote Similarity	NPD5988	Approved
0.6475	Remote Similarity	NPD6370	Approved
0.6471	Remote Similarity	NPD6082	Clinical (unspecified phase)
0.6471	Remote Similarity	NPD5363	Approved
0.6471	Remote Similarity	NPD6009	Approved
0.6471	Remote Similarity	NPD8295	Clinical (unspecified phase)
0.6465	Remote Similarity	NPD4252	Approved
0.6465	Remote Similarity	NPD5368	Approved
0.6458	Remote Similarity	NPD8039	Approved
0.6449	Remote Similarity	NPD7901	Clinical (unspecified phase)
0.6449	Remote Similarity	NPD7900	Approved
0.6449	Remote Similarity	NPD7748	Approved
0.6436	Remote Similarity	NPD7154	Phase 3
0.6435	Remote Similarity	NPD6014	Approved
0.6435	Remote Similarity	NPD6012	Approved
0.6435	Remote Similarity	NPD6013	Approved
0.6415	Remote Similarity	NPD7515	Phase 2
0.6415	Remote Similarity	NPD8034	Phase 2
0.6415	Remote Similarity	NPD8035	Phase 2
0.641	Remote Similarity	NPD8297	Approved
0.641	Remote Similarity	NPD6053	Discontinued
0.6408	Remote Similarity	NPD3618	Phase 1
0.6408	Remote Similarity	NPD4249	Approved
0.6404	Remote Similarity	NPD6412	Phase 2
0.6393	Remote Similarity	NPD5983	Phase 2
0.6385	Remote Similarity	NPD8387	Clinical (unspecified phase)
0.6381	Remote Similarity	NPD1695	Approved
0.6381	Remote Similarity	NPD5328	Approved
0.6379	Remote Similarity	NPD7102	Approved
0.6379	Remote Similarity	NPD7290	Approved
0.6379	Remote Similarity	NPD6883	Approved
0.6356	Remote Similarity	NPD8133	Approved
0.6346	Remote Similarity	NPD4251	Approved
0.6346	Remote Similarity	NPD4250	Approved
0.6337	Remote Similarity	NPD5209	Approved
0.6337	Remote Similarity	NPD3667	Approved
0.6336	Remote Similarity	NPD7966	Clinical (unspecified phase)
0.6325	Remote Similarity	NPD6617	Approved
0.6325	Remote Similarity	NPD8130	Phase 1
0.6325	Remote Similarity	NPD6869	Approved
0.6325	Remote Similarity	NPD6401	Clinical (unspecified phase)
0.6325	Remote Similarity	NPD6847	Approved
0.6308	Remote Similarity	NPD8415	Approved
0.6306	Remote Similarity	NPD6648	Approved
0.629	Remote Similarity	NPD7604	Phase 2
0.6275	Remote Similarity	NPD6110	Phase 1
0.6275	Remote Similarity	NPD5362	Discontinued
0.6273	Remote Similarity	NPD4755	Approved
0.6271	Remote Similarity	NPD6882	Approved
0.6262	Remote Similarity	NPD4810	Clinical (unspecified phase)
0.6262	Remote Similarity	NPD6079	Approved
0.626	Remote Similarity	NPD8444	Approved
0.623	Remote Similarity	NPD7516	Approved
0.622	Remote Similarity	NPD6033	Approved
0.6214	Remote Similarity	NPD4786	Approved
0.6195	Remote Similarity	NPD5211	Phase 2
0.619	Remote Similarity	NPD8451	Approved
0.619	Remote Similarity	NPD6336	Discontinued
0.6182	Remote Similarity	NPD5220	Clinical (unspecified phase)
0.6182	Remote Similarity	NPD5222	Approved
0.6182	Remote Similarity	NPD5221	Approved
0.6176	Remote Similarity	NPD4800	Clinical (unspecified phase)
0.6161	Remote Similarity	NPD5286	Approved
0.6161	Remote Similarity	NPD4696	Approved
0.6161	Remote Similarity	NPD5285	Approved
0.6161	Remote Similarity	NPD4700	Approved
0.616	Remote Similarity	NPD7642	Approved
0.6148	Remote Similarity	NPD7327	Approved
0.6148	Remote Similarity	NPD7328	Approved
0.6142	Remote Similarity	NPD8448	Approved
0.6139	Remote Similarity	NPD5790	Clinical (unspecified phase)
0.6129	Remote Similarity	NPD6291	Clinical (unspecified phase)
0.6126	Remote Similarity	NPD5173	Approved
0.6126	Remote Similarity	NPD6084	Phase 2
0.6126	Remote Similarity	NPD6083	Phase 2
0.6116	Remote Similarity	NPD6274	Approved
0.6106	Remote Similarity	NPD5223	Approved
0.6095	Remote Similarity	NPD6409	Approved
0.6095	Remote Similarity	NPD7334	Approved
0.6095	Remote Similarity	NPD7521	Approved
0.6095	Remote Similarity	NPD5330	Approved
0.6095	Remote Similarity	NPD6684	Approved
0.6095	Remote Similarity	NPD7146	Approved
0.6091	Remote Similarity	NPD5695	Phase 3
0.6087	Remote Similarity	NPD5141	Approved
0.6077	Remote Similarity	NPD7260	Phase 2
0.6075	Remote Similarity	NPD5370	Suspended
0.6071	Remote Similarity	NPD5696	Approved
0.6066	Remote Similarity	NPD6317	Approved
0.6058	Remote Similarity	NPD3666	Approved
0.6058	Remote Similarity	NPD3133	Approved
0.6058	Remote Similarity	NPD6400	Clinical (unspecified phase)
0.6058	Remote Similarity	NPD3665	Phase 1
0.6055	Remote Similarity	NPD4202	Approved
0.6053	Remote Similarity	NPD5225	Approved
0.6053	Remote Similarity	NPD4633	Approved
0.6053	Remote Similarity	NPD5224	Approved
0.6053	Remote Similarity	NPD5226	Approved
0.6048	Remote Similarity	NPD8377	Approved
0.6048	Remote Similarity	NPD8294	Approved
0.6038	Remote Similarity	NPD7524	Approved
0.6038	Remote Similarity	NPD3573	Approved
0.6034	Remote Similarity	NPD5048	Discontinued
0.6032	Remote Similarity	NPD7829	Approved
0.6032	Remote Similarity	NPD7830	Approved
0.6016	Remote Similarity	NPD6313	Approved
0.6016	Remote Similarity	NPD6314	Approved
0.6016	Remote Similarity	NPD6335	Approved
0.6	Remote Similarity	NPD8296	Approved
0.6	Remote Similarity	NPD8378	Approved
0.6	Remote Similarity	NPD8033	Approved
0.6	Remote Similarity	NPD8379	Approved
0.6	Remote Similarity	NPD4754	Approved
0.6	Remote Similarity	NPD5175	Approved
0.6	Remote Similarity	NPD8335	Approved
0.6	Remote Similarity	NPD5174	Approved
0.6	Remote Similarity	NPD7520	Clinical (unspecified phase)
0.6	Remote Similarity	NPD8392	Approved
0.6	Remote Similarity	NPD8380	Approved
0.6	Remote Similarity	NPD8391	Approved
0.6	Remote Similarity	NPD8390	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