NPASS Compound

Structure

NPC255428 OpenBabel07101718292D 27 29 0 0 1 0 0 0 0 0999 V2000 3.9899 -0.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1893 2.1590 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0380 0.9000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0878 -1.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0878 0.0570 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0878 -1.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0878 0.0570 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0000 -1.6180 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5878 -0.8090 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5878 -0.8090 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5878 -0.8090 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9511 -1.3090 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4899 0.1910 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9021 -0.6180 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9021 1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5443 1.6045 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9511 0.6910 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 0.9511 -0.3090 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.5878 -0.8090 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.7601 -1.8968 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.2111 -1.5691 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.1321 2.4135 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.0435 0.7955 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 3.4899 0.1910 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.2111 1.9511 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.4502 1.7091 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 24 1 0 0 0 0 2 25 1 0 0 0 0 3 26 1 0 0 0 0 4 6 1 0 0 0 0 4 9 2 0 0 0 0 5 7 2 0 0 0 0 5 9 1 0 0 0 0 6 10 2 0 0 0 0 7 10 1 0 0 0 0 8 11 2 0 0 0 0 8 12 1 0 0 0 0 9 11 1 0 0 0 0 10 19 1 0 0 0 0 11 27 1 0 0 0 0 12 20 2 0 0 0 0 13 14 1 0 0 0 0 13 15 2 0 0 0 0 13 24 1 0 0 0 0 14 18 1 0 0 0 0 14 21 2 0 0 0 0 15 17 1 0 0 0 0 15 25 1 0 0 0 0 16 17 1 0 0 0 0 16 22 2 0 0 0 0 16 26 1 0 0 0 0 17 18 1 1 0 0 0 17 23 1 0 0 0 0 18 12 1 1 0 0 0 18 27 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	376.08
Volume:	352.235
LogP:	1.693
LogD:	2.047
LogS:	-3.571
# Rotatable Bonds:	5
TPSA:	128.59
# H-Bond Aceptor:	9
# H-Bond Donor:	2
# Rings:	3
# Heavy Atoms:	9

MedChem Properties

QED Drug-Likeness Score:	0.554
Synthetic Accessibility Score:	4.498
Fsp3:	0.278
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Accepted
GSK Rule:	Accepted
BMS Rule:	0
Golden Triangle Rule:	Accepted
Chelating Alert:	1
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-5.259
MDCK Permeability:	2.541331014072057e-05
Pgp-inhibitor:	0.278
Pgp-substrate:	0.003
Human Intestinal Absorption (HIA):	0.729
20% Bioavailability (F20%):	0.999
30% Bioavailability (F30%):	0.997

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.819
Plasma Protein Binding (PPB):	74.67720794677734%
Volume Distribution (VD):	1.088
Pgp-substrate:	21.969457626342773%

ADMET: Metabolism

CYP1A2-inhibitor:	0.966
CYP1A2-substrate:	0.972
CYP2C19-inhibitor:	0.612
CYP2C19-substrate:	0.809
CYP2C9-inhibitor:	0.33
CYP2C9-substrate:	0.027
CYP2D6-inhibitor:	0.012
CYP2D6-substrate:	0.1
CYP3A4-inhibitor:	0.294
CYP3A4-substrate:	0.809

ADMET: Excretion

Clearance (CL):	3.099
Half-life (T1/2):	0.421

ADMET: Toxicity

hERG Blockers:	0.016
Human Hepatotoxicity (H-HT):	0.919
Drug-inuced Liver Injury (DILI):	0.987
AMES Toxicity:	0.315
Rat Oral Acute Toxicity:	0.057
Maximum Recommended Daily Dose:	0.014
Skin Sensitization:	0.354
Carcinogencity:	0.096
Eye Corrosion:	0.004
Eye Irritation:	0.049
Respiratory Toxicity:	0.149

Download Data

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

Natural Product: NPC255428

Natural Product ID:	NPC255428
*Common Name:**	Limnophilaspiroketone
IUPAC Name:	methyl (5S,9R)-9-hydroxy-2-(4-hydroxyphenyl)-7,8-dimethoxy-4,6-dioxo-1-oxaspiro[4.4]nona-2,7-diene-9-carboxylate
Synonyms:	Limnophilaspiroketone
Standard InCHIKey:	PDQUFOPZEHNTQQ-ROUUACIJSA-N
Standard InCHI:	InChI=1S/C18H16O9/c1-24-13-14(21)18(17(23,15(13)25-2)16(22)26-3)12(20)8-11(27-18)9-4-6-10(19)7-5-9/h4-8,19,23H,1-3H3/t17-,18-/m0/s1
SMILES:	COC1=C(OC)[C@]([C@]2(C1=O)OC(=CC2=O)c1ccc(cc1)O)(O)C(=O)OC
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL512128
PubChem CID:	11428821
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0002448] Benzenoids [CHEMONTID:0000134] Phenols [CHEMONTID:0004646] 1-hydroxy-2-unsubstituted benzenoids

*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
NPO9458	Limnophila geoffrayi	Species	Limoniidae	Eukaryota	n.a.	n.a.	n.a.	PMID[16038568]

☑ 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
Individual Protein	1

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT935	Individual Protein	Quinone reductase 1)	Homo sapiens	CD	>	20.0	ug ml-1	PMID[550547]

☑ 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 NPC255428 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	296
0.1-0.2	1294
0.2-0.3	3963
0.3-0.4	8878
0.4-0.5	9541
0.5-0.6	5534
0.6-0.7	11873
0.7-0.8	1309
0.8-0.85	6
0.85-0.9	2
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
0.8662	High Similarity	NPC32
0.8662	High Similarity	NPC122491
0.838	Intermediate Similarity	NPC59775
0.838	Intermediate Similarity	NPC256162
0.8345	Intermediate Similarity	NPC215484
0.8311	Intermediate Similarity	NPC32197
0.8092	Intermediate Similarity	NPC477299
0.8071	Intermediate Similarity	NPC108553
0.8041	Intermediate Similarity	NPC475539
0.8041	Intermediate Similarity	NPC119773
0.8041	Intermediate Similarity	NPC143246
0.8041	Intermediate Similarity	NPC474268
0.8027	Intermediate Similarity	NPC63304
0.8015	Intermediate Similarity	NPC14141
0.8013	Intermediate Similarity	NPC474620
0.7973	Intermediate Similarity	NPC475528
0.7972	Intermediate Similarity	NPC70680
0.7972	Intermediate Similarity	NPC233350
0.7972	Intermediate Similarity	NPC182217
0.7943	Intermediate Similarity	NPC281798
0.7922	Intermediate Similarity	NPC317585
0.7902	Intermediate Similarity	NPC68517
0.7902	Intermediate Similarity	NPC474895
0.7887	Intermediate Similarity	NPC323379
0.7887	Intermediate Similarity	NPC327204
0.7877	Intermediate Similarity	NPC156709
0.7877	Intermediate Similarity	NPC179505
0.7867	Intermediate Similarity	NPC143892
0.7867	Intermediate Similarity	NPC221383
0.7867	Intermediate Similarity	NPC299090
0.7867	Intermediate Similarity	NPC229264
0.7867	Intermediate Similarity	NPC283081
0.7852	Intermediate Similarity	NPC210330
0.7832	Intermediate Similarity	NPC477280
0.7832	Intermediate Similarity	NPC19719
0.7832	Intermediate Similarity	NPC477281
0.7815	Intermediate Similarity	NPC471076
0.7815	Intermediate Similarity	NPC192568
0.7808	Intermediate Similarity	NPC283560
0.7808	Intermediate Similarity	NPC24295
0.7808	Intermediate Similarity	NPC220936
0.7808	Intermediate Similarity	NPC31745
0.7793	Intermediate Similarity	NPC472132
0.7785	Intermediate Similarity	NPC304956
0.777	Intermediate Similarity	NPC132921
0.7756	Intermediate Similarity	NPC475378
0.7755	Intermediate Similarity	NPC274891
0.7755	Intermediate Similarity	NPC476819
0.7755	Intermediate Similarity	NPC205751
0.7755	Intermediate Similarity	NPC303683
0.7755	Intermediate Similarity	NPC26241
0.7755	Intermediate Similarity	NPC474875
0.7755	Intermediate Similarity	NPC476820
0.7755	Intermediate Similarity	NPC295492
0.7748	Intermediate Similarity	NPC322660
0.7746	Intermediate Similarity	NPC32626
0.7746	Intermediate Similarity	NPC237506
0.7746	Intermediate Similarity	NPC217052
0.7746	Intermediate Similarity	NPC329344
0.7744	Intermediate Similarity	NPC216387
0.774	Intermediate Similarity	NPC67349
0.774	Intermediate Similarity	NPC279676
0.7736	Intermediate Similarity	NPC164937
0.7733	Intermediate Similarity	NPC53884
0.7733	Intermediate Similarity	NPC258671
0.773	Intermediate Similarity	NPC217431
0.7727	Intermediate Similarity	NPC246566
0.7727	Intermediate Similarity	NPC95498
0.7714	Intermediate Similarity	NPC251407
0.7714	Intermediate Similarity	NPC168653
0.7714	Intermediate Similarity	NPC475695
0.7687	Intermediate Similarity	NPC278068
0.7687	Intermediate Similarity	NPC302857
0.7687	Intermediate Similarity	NPC219428
0.7687	Intermediate Similarity	NPC37250
0.7687	Intermediate Similarity	NPC152942
0.7687	Intermediate Similarity	NPC142703
0.7682	Intermediate Similarity	NPC98356
0.7681	Intermediate Similarity	NPC469927
0.7676	Intermediate Similarity	NPC214246
0.7676	Intermediate Similarity	NPC253595
0.7676	Intermediate Similarity	NPC469549
0.7673	Intermediate Similarity	NPC317544
0.7671	Intermediate Similarity	NPC317045
0.7671	Intermediate Similarity	NPC246177
0.7671	Intermediate Similarity	NPC71638
0.7671	Intermediate Similarity	NPC64230
0.7669	Intermediate Similarity	NPC469509
0.7667	Intermediate Similarity	NPC183824
0.7667	Intermediate Similarity	NPC474692
0.7655	Intermediate Similarity	NPC106406
0.7655	Intermediate Similarity	NPC471029
0.764	Intermediate Similarity	NPC180586
0.7635	Intermediate Similarity	NPC147379
0.7628	Intermediate Similarity	NPC137301
0.7628	Intermediate Similarity	NPC478231
0.7603	Intermediate Similarity	NPC311742
0.76	Intermediate Similarity	NPC152796
0.76	Intermediate Similarity	NPC475213
0.76	Intermediate Similarity	NPC186296
0.76	Intermediate Similarity	NPC277315
0.76	Intermediate Similarity	NPC258469
0.76	Intermediate Similarity	NPC285550
0.76	Intermediate Similarity	NPC319628
0.76	Intermediate Similarity	NPC37331
0.76	Intermediate Similarity	NPC43158
0.76	Intermediate Similarity	NPC220664
0.76	Intermediate Similarity	NPC192831
0.76	Intermediate Similarity	NPC284948
0.76	Intermediate Similarity	NPC303090
0.76	Intermediate Similarity	NPC472016
0.7595	Intermediate Similarity	NPC475663
0.7595	Intermediate Similarity	NPC472889
0.7595	Intermediate Similarity	NPC286919
0.7589	Intermediate Similarity	NPC61181
0.7589	Intermediate Similarity	NPC147192
0.7586	Intermediate Similarity	NPC168799
0.7586	Intermediate Similarity	NPC155209
0.7586	Intermediate Similarity	NPC202743
0.7584	Intermediate Similarity	NPC154262
0.7584	Intermediate Similarity	NPC7518
0.7584	Intermediate Similarity	NPC137501
0.7584	Intermediate Similarity	NPC230902
0.7584	Intermediate Similarity	NPC159387
0.7584	Intermediate Similarity	NPC477279
0.758	Intermediate Similarity	NPC478230
0.758	Intermediate Similarity	NPC69043
0.758	Intermediate Similarity	NPC471456
0.758	Intermediate Similarity	NPC170189
0.758	Intermediate Similarity	NPC472890
0.758	Intermediate Similarity	NPC478221
0.758	Intermediate Similarity	NPC208173
0.7574	Intermediate Similarity	NPC311091
0.7574	Intermediate Similarity	NPC471033
0.7568	Intermediate Similarity	NPC73078
0.7568	Intermediate Similarity	NPC148738
0.7568	Intermediate Similarity	NPC327612
0.7568	Intermediate Similarity	NPC319870
0.7568	Intermediate Similarity	NPC220942
0.7568	Intermediate Similarity	NPC49597
0.7564	Intermediate Similarity	NPC115249
0.7564	Intermediate Similarity	NPC327225
0.7564	Intermediate Similarity	NPC478224
0.7564	Intermediate Similarity	NPC76041
0.7564	Intermediate Similarity	NPC184284
0.755	Intermediate Similarity	NPC77922
0.755	Intermediate Similarity	NPC473281
0.7548	Intermediate Similarity	NPC56204
0.7548	Intermediate Similarity	NPC164762
0.7548	Intermediate Similarity	NPC116822
0.7548	Intermediate Similarity	NPC472891
0.7547	Intermediate Similarity	NPC469384
0.7547	Intermediate Similarity	NPC76211
0.7537	Intermediate Similarity	NPC221870
0.7535	Intermediate Similarity	NPC103533
0.7534	Intermediate Similarity	NPC169398
0.7533	Intermediate Similarity	NPC35702
0.7533	Intermediate Similarity	NPC297517
0.7533	Intermediate Similarity	NPC253722
0.7533	Intermediate Similarity	NPC31751
0.7533	Intermediate Similarity	NPC206095
0.7533	Intermediate Similarity	NPC224389
0.7533	Intermediate Similarity	NPC477335
0.7533	Intermediate Similarity	NPC13818
0.7533	Intermediate Similarity	NPC477278
0.7533	Intermediate Similarity	NPC471027
0.7533	Intermediate Similarity	NPC253481
0.7533	Intermediate Similarity	NPC477277
0.7532	Intermediate Similarity	NPC478234
0.7532	Intermediate Similarity	NPC123208
0.7517	Intermediate Similarity	NPC173034
0.7517	Intermediate Similarity	NPC302844
0.7517	Intermediate Similarity	NPC61
0.7517	Intermediate Similarity	NPC18074
0.7517	Intermediate Similarity	NPC5419
0.7517	Intermediate Similarity	NPC288452
0.7517	Intermediate Similarity	NPC289690
0.7517	Intermediate Similarity	NPC25581
0.75	Intermediate Similarity	NPC91809
0.75	Intermediate Similarity	NPC308976
0.75	Intermediate Similarity	NPC200773
0.75	Intermediate Similarity	NPC223185
0.75	Intermediate Similarity	NPC212541
0.75	Intermediate Similarity	NPC240768
0.75	Intermediate Similarity	NPC236981
0.7484	Intermediate Similarity	NPC44378
0.7484	Intermediate Similarity	NPC117346
0.7484	Intermediate Similarity	NPC84142
0.7484	Intermediate Similarity	NPC473395
0.7484	Intermediate Similarity	NPC478225
0.7484	Intermediate Similarity	NPC240592
0.7484	Intermediate Similarity	NPC280753
0.7484	Intermediate Similarity	NPC329997
0.7484	Intermediate Similarity	NPC40920
0.7484	Intermediate Similarity	NPC223335
0.7483	Intermediate Similarity	NPC293154
0.7468	Intermediate Similarity	NPC210320
0.7468	Intermediate Similarity	NPC1580
0.7468	Intermediate Similarity	NPC189631
0.7468	Intermediate Similarity	NPC99381

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 NPC255428 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	256
0.1-0.2	779
0.2-0.3	1859
0.3-0.4	2843
0.4-0.5	1899
0.5-0.6	1112
0.6-0.7	382
0.7-0.8	20
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
0.76	Intermediate Similarity	NPD6190	Approved
0.7445	Intermediate Similarity	NPD9545	Approved
0.7407	Intermediate Similarity	NPD690	Clinical (unspecified phase)
0.7386	Intermediate Similarity	NPD6799	Approved
0.7267	Intermediate Similarity	NPD7075	Discontinued
0.723	Intermediate Similarity	NPD230	Phase 1
0.7215	Intermediate Similarity	NPD6599	Discontinued
0.7211	Intermediate Similarity	NPD6233	Phase 2
0.7143	Intermediate Similarity	NPD3764	Approved
0.7143	Intermediate Similarity	NPD3817	Phase 2
0.7125	Intermediate Similarity	NPD6801	Discontinued
0.7114	Intermediate Similarity	NPD6355	Discontinued
0.7103	Intermediate Similarity	NPD5647	Approved
0.7099	Intermediate Similarity	NPD3882	Suspended
0.7081	Intermediate Similarity	NPD7972	Discontinued
0.7081	Intermediate Similarity	NPD7096	Clinical (unspecified phase)
0.7078	Intermediate Similarity	NPD4628	Phase 3
0.7075	Intermediate Similarity	NPD7095	Approved
0.7051	Intermediate Similarity	NPD6143	Clinical (unspecified phase)
0.705	Intermediate Similarity	NPD9493	Approved
0.7047	Intermediate Similarity	NPD7966	Clinical (unspecified phase)
0.7037	Intermediate Similarity	NPD2067	Discontinued
0.7027	Intermediate Similarity	NPD6798	Discontinued
0.7025	Intermediate Similarity	NPD5403	Approved
0.7015	Intermediate Similarity	NPD1358	Approved
0.7014	Intermediate Similarity	NPD4379	Clinical (unspecified phase)
0.7006	Intermediate Similarity	NPD4378	Clinical (unspecified phase)
0.7	Intermediate Similarity	NPD4340	Discontinued
0.6994	Remote Similarity	NPD8055	Clinical (unspecified phase)
0.698	Remote Similarity	NPD4062	Phase 3
0.6974	Remote Similarity	NPD7033	Discontinued
0.6954	Remote Similarity	NPD6653	Approved
0.6948	Remote Similarity	NPD970	Clinical (unspecified phase)
0.6934	Remote Similarity	NPD969	Suspended
0.6933	Remote Similarity	NPD4060	Phase 1
0.6933	Remote Similarity	NPD5402	Approved
0.6913	Remote Similarity	NPD6859	Clinical (unspecified phase)
0.6899	Remote Similarity	NPD2532	Approved
0.6899	Remote Similarity	NPD5401	Approved
0.6899	Remote Similarity	NPD2534	Approved
0.6899	Remote Similarity	NPD2533	Approved
0.6894	Remote Similarity	NPD4380	Phase 2
0.6886	Remote Similarity	NPD6232	Discontinued
0.6883	Remote Similarity	NPD7266	Discontinued
0.6875	Remote Similarity	NPD422	Phase 1
0.6871	Remote Similarity	NPD2801	Approved
0.6864	Remote Similarity	NPD7473	Discontinued
0.686	Remote Similarity	NPD7685	Pre-registration
0.6859	Remote Similarity	NPD1878	Clinical (unspecified phase)
0.6849	Remote Similarity	NPD3225	Approved
0.6839	Remote Similarity	NPD2424	Discontinued
0.6828	Remote Similarity	NPD9717	Approved
0.6821	Remote Similarity	NPD4338	Clinical (unspecified phase)
0.6821	Remote Similarity	NPD1240	Approved
0.6818	Remote Similarity	NPD2935	Discontinued
0.6815	Remote Similarity	NPD2354	Approved
0.6815	Remote Similarity	NPD3134	Approved
0.6803	Remote Similarity	NPD987	Approved
0.68	Remote Similarity	NPD3268	Approved
0.6798	Remote Similarity	NPD7879	Clinical (unspecified phase)
0.6797	Remote Similarity	NPD7097	Phase 1
0.6795	Remote Similarity	NPD7421	Clinical (unspecified phase)
0.6784	Remote Similarity	NPD7804	Clinical (unspecified phase)
0.6776	Remote Similarity	NPD447	Suspended
0.6774	Remote Similarity	NPD6003	Clinical (unspecified phase)
0.6774	Remote Similarity	NPD6004	Phase 3
0.6774	Remote Similarity	NPD6002	Phase 3
0.6774	Remote Similarity	NPD6006	Clinical (unspecified phase)
0.6774	Remote Similarity	NPD2344	Approved
0.6774	Remote Similarity	NPD6005	Phase 3
0.6765	Remote Similarity	NPD9265	Clinical (unspecified phase)
0.6761	Remote Similarity	NPD8434	Phase 2
0.6753	Remote Similarity	NPD2799	Discontinued
0.675	Remote Similarity	NPD1512	Approved
0.6748	Remote Similarity	NPD7411	Suspended
0.6747	Remote Similarity	NPD4381	Clinical (unspecified phase)
0.6738	Remote Similarity	NPD4198	Discontinued
0.6736	Remote Similarity	NPD1778	Approved
0.6732	Remote Similarity	NPD1607	Approved
0.6728	Remote Similarity	NPD3226	Approved
0.6725	Remote Similarity	NPD3751	Discontinued
0.6707	Remote Similarity	NPD1934	Approved
0.6707	Remote Similarity	NPD6234	Discontinued
0.6706	Remote Similarity	NPD6167	Clinical (unspecified phase)
0.6706	Remote Similarity	NPD6166	Phase 2
0.6706	Remote Similarity	NPD6168	Clinical (unspecified phase)
0.6705	Remote Similarity	NPD6797	Phase 2
0.669	Remote Similarity	NPD3847	Discontinued
0.6689	Remote Similarity	NPD1203	Approved
0.6689	Remote Similarity	NPD2797	Approved
0.6689	Remote Similarity	NPD6362	Approved
0.6688	Remote Similarity	NPD2800	Approved
0.6687	Remote Similarity	NPD4868	Clinical (unspecified phase)
0.6687	Remote Similarity	NPD7410	Clinical (unspecified phase)
0.6667	Remote Similarity	NPD2393	Clinical (unspecified phase)
0.6667	Remote Similarity	NPD1550	Clinical (unspecified phase)
0.6667	Remote Similarity	NPD1552	Clinical (unspecified phase)
0.6667	Remote Similarity	NPD7819	Suspended
0.6667	Remote Similarity	NPD7251	Discontinued
0.6647	Remote Similarity	NPD7184	Clinical (unspecified phase)
0.6647	Remote Similarity	NPD3749	Approved
0.6646	Remote Similarity	NPD3750	Approved
0.6645	Remote Similarity	NPD1510	Phase 2
0.6645	Remote Similarity	NPD651	Clinical (unspecified phase)
0.6644	Remote Similarity	NPD1535	Discovery
0.6643	Remote Similarity	NPD7843	Approved
0.6643	Remote Similarity	NPD5536	Phase 2
0.6629	Remote Similarity	NPD7808	Phase 3
0.6628	Remote Similarity	NPD3818	Discontinued
0.6625	Remote Similarity	NPD1511	Approved
0.6624	Remote Similarity	NPD5958	Discontinued
0.6624	Remote Similarity	NPD1549	Phase 2
0.6624	Remote Similarity	NPD4534	Discontinued
0.6621	Remote Similarity	NPD4626	Approved
0.662	Remote Similarity	NPD7157	Approved
0.6604	Remote Similarity	NPD3887	Approved
0.6604	Remote Similarity	NPD2309	Approved
0.6603	Remote Similarity	NPD1551	Phase 2
0.66	Remote Similarity	NPD9494	Approved
0.6599	Remote Similarity	NPD1608	Approved
0.6599	Remote Similarity	NPD1481	Phase 2
0.6599	Remote Similarity	NPD9269	Phase 2
0.6594	Remote Similarity	NPD2684	Approved
0.6588	Remote Similarity	NPD3787	Discontinued
0.6587	Remote Similarity	NPD4967	Phase 2
0.6587	Remote Similarity	NPD4965	Approved
0.6587	Remote Similarity	NPD4966	Approved
0.6582	Remote Similarity	NPD1652	Phase 2
0.6575	Remote Similarity	NPD3496	Discontinued
0.6573	Remote Similarity	NPD8150	Discontinued
0.6561	Remote Similarity	NPD2353	Approved
0.6561	Remote Similarity	NPD5762	Approved
0.6561	Remote Similarity	NPD2355	Clinical (unspecified phase)
0.6561	Remote Similarity	NPD5763	Approved
0.6556	Remote Similarity	NPD6832	Phase 2
0.655	Remote Similarity	NPD3926	Phase 2
0.6543	Remote Similarity	NPD5049	Phase 3
0.6541	Remote Similarity	NPD8166	Discontinued
0.6541	Remote Similarity	NPD6398	Clinical (unspecified phase)
0.6533	Remote Similarity	NPD6007	Clinical (unspecified phase)
0.6531	Remote Similarity	NPD1091	Approved
0.6527	Remote Similarity	NPD8443	Clinical (unspecified phase)
0.6519	Remote Similarity	NPD7296	Approved
0.6516	Remote Similarity	NPD6651	Approved
0.6514	Remote Similarity	NPD7993	Clinical (unspecified phase)
0.6513	Remote Similarity	NPD2598	Clinical (unspecified phase)
0.6513	Remote Similarity	NPD3027	Phase 3
0.6512	Remote Similarity	NPD7852	Clinical (unspecified phase)
0.6506	Remote Similarity	NPD37	Approved
0.6503	Remote Similarity	NPD6980	Clinical (unspecified phase)
0.6494	Remote Similarity	NPD7054	Approved
0.6488	Remote Similarity	NPD7768	Phase 2
0.6486	Remote Similarity	NPD3972	Approved
0.6483	Remote Similarity	NPD1894	Discontinued
0.6481	Remote Similarity	NPD3536	Discontinued
0.6479	Remote Similarity	NPD1241	Discontinued
0.6477	Remote Similarity	NPD6559	Discontinued
0.6475	Remote Similarity	NPD74	Approved
0.6475	Remote Similarity	NPD9266	Approved
0.6475	Remote Similarity	NPD2182	Approved
0.6471	Remote Similarity	NPD6647	Phase 2
0.6471	Remote Similarity	NPD2313	Discontinued
0.6471	Remote Similarity	NPD1048	Approved
0.6467	Remote Similarity	NPD3267	Approved
0.6467	Remote Similarity	NPD3266	Approved
0.6463	Remote Similarity	NPD1653	Approved
0.6458	Remote Similarity	NPD694	Clinical (unspecified phase)
0.6457	Remote Similarity	NPD7074	Phase 3
0.6457	Remote Similarity	NPD7472	Approved
0.6454	Remote Similarity	NPD228	Approved
0.6452	Remote Similarity	NPD5124	Phase 1
0.6452	Remote Similarity	NPD5123	Clinical (unspecified phase)
0.6438	Remote Similarity	NPD5585	Approved
0.6438	Remote Similarity	NPD5691	Approved
0.6438	Remote Similarity	NPD9268	Approved
0.6437	Remote Similarity	NPD7228	Approved
0.6436	Remote Similarity	NPD7435	Discontinued
0.6433	Remote Similarity	NPD7199	Phase 2
0.6424	Remote Similarity	NPD1019	Discontinued
0.642	Remote Similarity	NPD4357	Discontinued
0.642	Remote Similarity	NPD5953	Discontinued
0.6419	Remote Similarity	NPD3705	Approved
0.6412	Remote Similarity	NPD5537	Clinical (unspecified phase)
0.6412	Remote Similarity	NPD919	Approved
0.6409	Remote Similarity	NPD8397	Clinical (unspecified phase)
0.6408	Remote Similarity	NPD5535	Approved
0.6403	Remote Similarity	NPD290	Approved
0.6403	Remote Similarity	NPD9264	Approved
0.6403	Remote Similarity	NPD9263	Approved
0.6403	Remote Similarity	NPD9267	Approved
0.6402	Remote Similarity	NPD920	Approved
0.64	Remote Similarity	NPD1876	Approved
0.6395	Remote Similarity	NPD17	Approved
0.6392	Remote Similarity	NPD2796	Approved
0.6387	Remote Similarity	NPD943	Approved
0.6382	Remote Similarity	NPD5736	Approved
0.638	Remote Similarity	NPD3688	Clinical (unspecified phase)
0.638	Remote Similarity	NPD3146	Approved
0.6369	Remote Similarity	NPD8455	Phase 2
0.6369	Remote Similarity	NPD1465	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