NPASS Compound

Structure

CID112706 OpenBabel06191715462D 23 25 0 0 1 0 0 0 0 0999 V2000 -2.5981 1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5254 0.6088 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8660 0.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 -2.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8660 -1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8660 -1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8660 1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9568 -1.2247 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6516 -0.6741 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0000 1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9909 -0.9659 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1056 0.2169 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5075 0.4701 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7321 1.0000 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.6639 -0.5176 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8660 -0.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8660 -0.5000 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 1.7321 -0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7321 -0.0000 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 0.0000 -0.0000 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 2.5981 -0.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.7321 1.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.3985 0.9240 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1 14 1 0 0 0 0 4 5 1 0 0 0 0 4 6 1 0 0 0 0 5 16 2 0 0 0 0 6 17 1 0 0 0 0 7 10 1 0 0 0 0 7 14 1 0 0 0 0 8 11 1 0 0 0 0 8 15 1 0 0 0 0 9 12 2 0 0 0 0 9 15 1 0 0 0 0 10 20 1 0 0 0 0 11 19 1 0 0 0 0 12 23 1 0 0 0 0 13 15 2 0 0 0 0 13 23 1 0 0 0 0 14 19 1 1 0 0 0 16 18 1 0 0 0 0 16 20 1 0 0 0 0 17 19 1 1 0 0 0 17 20 1 0 0 0 0 18 21 2 0 0 0 0 18 22 1 0 0 0 0 19 2 1 1 0 0 0 20 3 1 1 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	316.2
Volume:	344.632
LogP:	4.921
LogD:	4.33
LogS:	-4.286
# Rotatable Bonds:	4
TPSA:	50.44
# H-Bond Aceptor:	3
# H-Bond Donor:	1
# Rings:	3
# Heavy Atoms:	3

MedChem Properties

QED Drug-Likeness Score:	0.843
Synthetic Accessibility Score:	4.167
Fsp3:	0.65
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:	-4.812
MDCK Permeability:	2.7456813768367283e-05
Pgp-inhibitor:	0.924
Pgp-substrate:	0.005
Human Intestinal Absorption (HIA):	0.009
20% Bioavailability (F20%):	0.713
30% Bioavailability (F30%):	0.8

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.171
Plasma Protein Binding (PPB):	96.53935241699219%
Volume Distribution (VD):	1.376
Pgp-substrate:	2.71787428855896%

ADMET: Metabolism

CYP1A2-inhibitor:	0.116
CYP1A2-substrate:	0.213
CYP2C19-inhibitor:	0.08
CYP2C19-substrate:	0.3
CYP2C9-inhibitor:	0.352
CYP2C9-substrate:	0.158
CYP2D6-inhibitor:	0.107
CYP2D6-substrate:	0.551
CYP3A4-inhibitor:	0.483
CYP3A4-substrate:	0.226

ADMET: Excretion

Clearance (CL):	9.071
Half-life (T1/2):	0.443

ADMET: Toxicity

hERG Blockers:	0.057
Human Hepatotoxicity (H-HT):	0.765
Drug-inuced Liver Injury (DILI):	0.028
AMES Toxicity:	0.008
Rat Oral Acute Toxicity:	0.959
Maximum Recommended Daily Dose:	0.799
Skin Sensitization:	0.822
Carcinogencity:	0.916
Eye Corrosion:	0.192
Eye Irritation:	0.65
Respiratory Toxicity:	0.981

Download Data

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

Natural Product: NPC112706

Natural Product ID:	NPC112706
*Common Name:**	(+)-Hardwickiic Acid
IUPAC Name:	(4aS,5R,6S,8aS)-5-[2-(furan-3-yl)ethyl]-5,6,8a-trimethyl-3,4,4a,6,7,8-hexahydronaphthalene-1-carboxylic acid
Synonyms:	(+)-Hardwickiic Acid
Standard InCHIKey:	HHWOKJDCJVESIF-GIPAHHNCSA-N
Standard InCHI:	InChI=1S/C20H28O3/c1-14-7-10-20(3)16(18(21)22)5-4-6-17(20)19(14,2)11-8-15-9-12-23-13-15/h5,9,12-14,17H,4,6-8,10-11H2,1-3H3,(H,21,22)/p-1/t14-,17-,19+,20+/m0/s1
SMILES:	C[C@H]1CC[C@]2(C)C(=CCC[C@H]2[C@]1(C)CCc1ccoc1)C(=O)[O-]
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL319344
PubChem CID:	161454
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001551] Diterpenoids [CHEMONTID:0001757] Colensane and clerodane diterpenoids

*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
NPO22719	Jodina rhombifolia	Species	Cervantesiaceae	Eukaryota	n.a.	seed	n.a.	DOI[10.1007/BF02541352]
NPO22956	Cervus nippon	Species	Cervidae	Eukaryota	n.a.	n.a.	n.a.	PMID[15112737]
NPO11802	Physeter catodon	Species	Physeteridae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO22956	Cervus nippon	Species	Cervidae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO30253	Duranta repens	Species	Verbenaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO11802	Physeter catodon	Species	Physeteridae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO30253	Duranta repens	Species	Verbenaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO11802	Physeter catodon	Species	Physeteridae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO22956	Cervus nippon	Species	Cervidae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO22956	Cervus nippon	Species	Cervidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO22776	Copaifera officinalis	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO16747	Helianthus decapetalus	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO20397	Glycosmis mauritiana	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO10341	Pseudogymnoascus pannorum	Species	Pseudeurotiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO23064	Eranthis hyemalis	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO11802	Physeter catodon	Species	Physeteridae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO22833	Pecten aurantiacus	Species	Pectinidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO22719	Jodina rhombifolia	Species	Cervantesiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO23185	Xanthium indicum	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO22017	Haemanthus kalbreyeri	Species	Amaryllidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO22257	Centaurea rhaetica	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO22139	Leucocoprinus birnbaumii	Species	Agaricaceae	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
MIC	2
Others	4

Activity Type	# Activity
Organism	6

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT32	Organism	Mus musculus	Mus musculus	Change in body weight	=	1.6	g	PMID[468341]
NPT32	Organism	Mus musculus	Mus musculus	Life span	=	14.8	day	PMID[468341]
NPT32	Organism	Mus musculus	Mus musculus	ILS	=	17.0	%	PMID[468341]
NPT79	Organism	Bacillus subtilis	Bacillus subtilis	IZ	=	10.0	mm	PMID[468342]
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	MIC	=	25.0	ug.mL-1	PMID[468342]
NPT79	Organism	Bacillus subtilis	Bacillus subtilis	MIC	=	12.5	ug.mL-1	PMID[468342]

☑ 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 NPC112706 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	220
0.1-0.2	1271
0.2-0.3	2720
0.3-0.4	6245
0.4-0.5	12191
0.5-0.6	11267
0.6-0.7	7780
0.7-0.8	789
0.8-0.85	144
0.85-0.9	47
0.9-0.95	17
0.95-1	6

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC207294
0.9752	High Similarity	NPC83178
0.9669	High Similarity	NPC46536
0.9669	High Similarity	NPC138139
0.9669	High Similarity	NPC23086
0.9421	High Similarity	NPC16922
0.9286	High Similarity	NPC89133
0.9268	High Similarity	NPC179354
0.9194	High Similarity	NPC74612
0.9187	High Similarity	NPC243269
0.9187	High Similarity	NPC130275
0.918	High Similarity	NPC477967
0.916	High Similarity	NPC90953
0.9134	High Similarity	NPC61788
0.9048	High Similarity	NPC477966
0.9048	High Similarity	NPC477123
0.8992	High Similarity	NPC218838
0.8984	High Similarity	NPC298190
0.8968	High Similarity	NPC290955
0.8926	High Similarity	NPC208906
0.8926	High Similarity	NPC144745
0.8917	High Similarity	NPC150895
0.8898	High Similarity	NPC477039
0.8898	High Similarity	NPC477040
0.8872	High Similarity	NPC202260
0.8871	High Similarity	NPC36255
0.8855	High Similarity	NPC158525
0.8852	High Similarity	NPC243704
0.8828	High Similarity	NPC223063
0.8828	High Similarity	NPC120836
0.8819	High Similarity	NPC246392
0.8806	High Similarity	NPC148374
0.88	High Similarity	NPC272899
0.8788	High Similarity	NPC146872
0.876	High Similarity	NPC476925
0.875	High Similarity	NPC279877
0.875	High Similarity	NPC327527
0.875	High Similarity	NPC26532
0.875	High Similarity	NPC476917
0.873	High Similarity	NPC477038
0.873	High Similarity	NPC477965
0.873	High Similarity	NPC83115
0.8722	High Similarity	NPC310830
0.872	High Similarity	NPC317217
0.8712	High Similarity	NPC92941
0.8712	High Similarity	NPC476947
0.8702	High Similarity	NPC470740
0.8696	High Similarity	NPC346
0.8686	High Similarity	NPC476944
0.8682	High Similarity	NPC208389
0.8676	High Similarity	NPC121158
0.8661	High Similarity	NPC230979
0.8661	High Similarity	NPC303010
0.8647	High Similarity	NPC46896
0.8633	High Similarity	NPC250228
0.8618	High Similarity	NPC212918
0.8613	High Similarity	NPC267632
0.8605	High Similarity	NPC329707
0.8582	High Similarity	NPC470742
0.8582	High Similarity	NPC307401
0.8561	High Similarity	NPC471006
0.8551	High Similarity	NPC251865
0.8538	High Similarity	NPC59502
0.8529	High Similarity	NPC56197
0.8519	High Similarity	NPC476943
0.8519	High Similarity	NPC236532
0.8519	High Similarity	NPC220094
0.8512	High Similarity	NPC1811
0.8512	High Similarity	NPC26157
0.85	High Similarity	NPC471174
0.8496	Intermediate Similarity	NPC471998
0.8485	Intermediate Similarity	NPC471817
0.8467	Intermediate Similarity	NPC205765
0.8462	Intermediate Similarity	NPC474438
0.8462	Intermediate Similarity	NPC474279
0.8444	Intermediate Similarity	NPC170604
0.8444	Intermediate Similarity	NPC215109
0.8444	Intermediate Similarity	NPC42400
0.844	Intermediate Similarity	NPC476941
0.844	Intermediate Similarity	NPC476942
0.8438	Intermediate Similarity	NPC65735
0.8438	Intermediate Similarity	NPC118853
0.8438	Intermediate Similarity	NPC188377
0.84	Intermediate Similarity	NPC87466
0.8397	Intermediate Similarity	NPC198904
0.8394	Intermediate Similarity	NPC90296
0.8394	Intermediate Similarity	NPC67003
0.8385	Intermediate Similarity	NPC95567
0.8385	Intermediate Similarity	NPC476016
0.8385	Intermediate Similarity	NPC319140
0.838	Intermediate Similarity	NPC234494
0.8372	Intermediate Similarity	NPC71274
0.8372	Intermediate Similarity	NPC300098
0.8372	Intermediate Similarity	NPC473885
0.8372	Intermediate Similarity	NPC75557
0.8372	Intermediate Similarity	NPC474829
0.8372	Intermediate Similarity	NPC471074
0.8369	Intermediate Similarity	NPC216755
0.8369	Intermediate Similarity	NPC255414
0.8369	Intermediate Similarity	NPC476938
0.8369	Intermediate Similarity	NPC476937
0.8346	Intermediate Similarity	NPC473982
0.8346	Intermediate Similarity	NPC471995
0.8346	Intermediate Similarity	NPC97566
0.8345	Intermediate Similarity	NPC476946
0.8333	Intermediate Similarity	NPC33938
0.8322	Intermediate Similarity	NPC470997
0.8309	Intermediate Similarity	NPC186626
0.8308	Intermediate Similarity	NPC329922
0.8308	Intermediate Similarity	NPC474260
0.8308	Intermediate Similarity	NPC81912
0.8308	Intermediate Similarity	NPC329694
0.8286	Intermediate Similarity	NPC238843
0.8286	Intermediate Similarity	NPC142113
0.8286	Intermediate Similarity	NPC199044
0.8284	Intermediate Similarity	NPC293253
0.8279	Intermediate Similarity	NPC105249
0.8276	Intermediate Similarity	NPC30222
0.8273	Intermediate Similarity	NPC263337
0.8273	Intermediate Similarity	NPC52412
0.8264	Intermediate Similarity	NPC177331
0.8264	Intermediate Similarity	NPC272590
0.8252	Intermediate Similarity	NPC69647
0.8252	Intermediate Similarity	NPC195325
0.8252	Intermediate Similarity	NPC125182
0.8252	Intermediate Similarity	NPC472654
0.8248	Intermediate Similarity	NPC472376
0.8244	Intermediate Similarity	NPC474830
0.8231	Intermediate Similarity	NPC471559
0.8231	Intermediate Similarity	NPC290193
0.8227	Intermediate Similarity	NPC185456
0.8219	Intermediate Similarity	NPC35000
0.8217	Intermediate Similarity	NPC476351
0.8214	Intermediate Similarity	NPC243577
0.8214	Intermediate Similarity	NPC223415
0.8214	Intermediate Similarity	NPC470741
0.8207	Intermediate Similarity	NPC246164
0.8207	Intermediate Similarity	NPC469503
0.8207	Intermediate Similarity	NPC44577
0.8194	Intermediate Similarity	NPC228842
0.8194	Intermediate Similarity	NPC212257
0.8189	Intermediate Similarity	NPC473969
0.8182	Intermediate Similarity	NPC93666
0.8182	Intermediate Similarity	NPC471521
0.8182	Intermediate Similarity	NPC473356
0.8169	Intermediate Similarity	NPC471292
0.8151	Intermediate Similarity	NPC178932
0.8151	Intermediate Similarity	NPC57998
0.8151	Intermediate Similarity	NPC282445
0.8148	Intermediate Similarity	NPC474425
0.8148	Intermediate Similarity	NPC474407
0.8148	Intermediate Similarity	NPC474426
0.814	Intermediate Similarity	NPC289911
0.814	Intermediate Similarity	NPC283284
0.8125	Intermediate Similarity	NPC470998
0.8116	Intermediate Similarity	NPC471996
0.8112	Intermediate Similarity	NPC10088
0.8112	Intermediate Similarity	NPC302987
0.811	Intermediate Similarity	NPC21831
0.811	Intermediate Similarity	NPC187547
0.8108	Intermediate Similarity	NPC261597
0.8108	Intermediate Similarity	NPC470118
0.8099	Intermediate Similarity	NPC247221
0.8099	Intermediate Similarity	NPC5676
0.8095	Intermediate Similarity	NPC281258
0.8095	Intermediate Similarity	NPC296807
0.8095	Intermediate Similarity	NPC44675
0.8095	Intermediate Similarity	NPC155939
0.8095	Intermediate Similarity	NPC264943
0.8095	Intermediate Similarity	NPC141538
0.8095	Intermediate Similarity	NPC214541
0.8095	Intermediate Similarity	NPC469336
0.8095	Intermediate Similarity	NPC92979
0.8082	Intermediate Similarity	NPC476939
0.8082	Intermediate Similarity	NPC476940
0.8082	Intermediate Similarity	NPC121615
0.8082	Intermediate Similarity	NPC472672
0.8082	Intermediate Similarity	NPC294511
0.8082	Intermediate Similarity	NPC268905
0.8082	Intermediate Similarity	NPC75906
0.8077	Intermediate Similarity	NPC475818
0.8071	Intermediate Similarity	NPC20500
0.8062	Intermediate Similarity	NPC474136
0.806	Intermediate Similarity	NPC21460
0.8058	Intermediate Similarity	NPC474722
0.8054	Intermediate Similarity	NPC477403
0.8042	Intermediate Similarity	NPC262198
0.8042	Intermediate Similarity	NPC276676
0.8041	Intermediate Similarity	NPC469485
0.8031	Intermediate Similarity	NPC131801
0.8028	Intermediate Similarity	NPC137295
0.8027	Intermediate Similarity	NPC302054
0.8027	Intermediate Similarity	NPC253201
0.8027	Intermediate Similarity	NPC98206
0.8027	Intermediate Similarity	NPC237259
0.8027	Intermediate Similarity	NPC34421
0.8016	Intermediate Similarity	NPC28054
0.8015	Intermediate Similarity	NPC178382
0.8014	Intermediate Similarity	NPC473152
0.8	Intermediate Similarity	NPC473379

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 NPC112706 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	216
0.1-0.2	936
0.2-0.3	1657
0.3-0.4	2584
0.4-0.5	2247
0.5-0.6	1189
0.6-0.7	299
0.7-0.8	22
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
0.8058	Intermediate Similarity	NPD2343	Clinical (unspecified phase)
0.774	Intermediate Similarity	NPD6273	Approved
0.7733	Intermediate Similarity	NPD5761	Phase 2
0.7733	Intermediate Similarity	NPD5760	Phase 2
0.7639	Intermediate Similarity	NPD4628	Phase 3
0.7517	Intermediate Similarity	NPD7003	Approved
0.7413	Intermediate Similarity	NPD2799	Discontinued
0.7372	Intermediate Similarity	NPD2797	Approved
0.7286	Intermediate Similarity	NPD5952	Clinical (unspecified phase)
0.7279	Intermediate Similarity	NPD6398	Clinical (unspecified phase)
0.7239	Intermediate Similarity	NPD6764	Approved
0.7239	Intermediate Similarity	NPD6765	Approved
0.7237	Intermediate Similarity	NPD5808	Clinical (unspecified phase)
0.7229	Intermediate Similarity	NPD8434	Phase 2
0.7211	Intermediate Similarity	NPD7421	Clinical (unspecified phase)
0.7192	Intermediate Similarity	NPD2346	Discontinued
0.7192	Intermediate Similarity	NPD2344	Approved
0.7183	Intermediate Similarity	NPD8032	Phase 2
0.7176	Intermediate Similarity	NPD1241	Discontinued
0.7174	Intermediate Similarity	NPD1283	Approved
0.7172	Intermediate Similarity	NPD4308	Phase 3
0.7153	Intermediate Similarity	NPD3972	Approved
0.7153	Intermediate Similarity	NPD9717	Approved
0.7153	Intermediate Similarity	NPD1608	Approved
0.7133	Intermediate Similarity	NPD4140	Approved
0.7124	Intermediate Similarity	NPD7458	Discontinued
0.7123	Intermediate Similarity	NPD1551	Phase 2
0.7113	Intermediate Similarity	NPD3268	Approved
0.7113	Intermediate Similarity	NPD2313	Discontinued
0.7111	Intermediate Similarity	NPD5585	Approved
0.7092	Intermediate Similarity	NPD6832	Phase 2
0.7083	Intermediate Similarity	NPD6355	Discontinued
0.7077	Intermediate Similarity	NPD2181	Clinical (unspecified phase)
0.7071	Intermediate Similarity	NPD2798	Approved
0.7066	Intermediate Similarity	NPD6784	Approved
0.7066	Intermediate Similarity	NPD6785	Approved
0.7059	Intermediate Similarity	NPD3412	Clinical (unspecified phase)
0.7059	Intermediate Similarity	NPD1778	Approved
0.7054	Intermediate Similarity	NPD6831	Clinical (unspecified phase)
0.705	Intermediate Similarity	NPD1876	Approved
0.7047	Intermediate Similarity	NPD3750	Approved
0.7047	Intermediate Similarity	NPD4109	Clinical (unspecified phase)
0.7047	Intermediate Similarity	NPD4110	Phase 3
0.7007	Intermediate Similarity	NPD4476	Approved
0.7007	Intermediate Similarity	NPD4477	Approved
0.7007	Intermediate Similarity	NPD2935	Discontinued
0.7006	Intermediate Similarity	NPD5616	Clinical (unspecified phase)
0.7	Intermediate Similarity	NPD1203	Approved
0.7	Intermediate Similarity	NPD2309	Approved
0.6993	Remote Similarity	NPD3764	Approved
0.6992	Remote Similarity	NPD5951	Approved
0.6974	Remote Similarity	NPD7004	Clinical (unspecified phase)
0.6959	Remote Similarity	NPD6002	Phase 3
0.6959	Remote Similarity	NPD6005	Phase 3
0.6959	Remote Similarity	NPD6003	Clinical (unspecified phase)
0.6959	Remote Similarity	NPD6006	Clinical (unspecified phase)
0.6959	Remote Similarity	NPD6004	Phase 3
0.6959	Remote Similarity	NPD1471	Phase 3
0.6957	Remote Similarity	NPD1281	Approved
0.6954	Remote Similarity	NPD643	Clinical (unspecified phase)
0.6934	Remote Similarity	NPD4626	Approved
0.6934	Remote Similarity	NPD17	Approved
0.6933	Remote Similarity	NPD8166	Discontinued
0.6923	Remote Similarity	NPD7008	Discontinued
0.6912	Remote Similarity	NPD9545	Approved
0.6912	Remote Similarity	NPD1894	Discontinued
0.6903	Remote Similarity	NPD3226	Approved
0.6897	Remote Similarity	NPD2979	Phase 3
0.6897	Remote Similarity	NPD4307	Phase 2
0.6884	Remote Similarity	NPD3496	Discontinued
0.6883	Remote Similarity	NPD920	Approved
0.6875	Remote Similarity	NPD411	Approved
0.6875	Remote Similarity	NPD5537	Clinical (unspecified phase)
0.6863	Remote Similarity	NPD642	Clinical (unspecified phase)
0.6861	Remote Similarity	NPD5691	Approved
0.6859	Remote Similarity	NPD6599	Discontinued
0.6857	Remote Similarity	NPD4359	Approved
0.6835	Remote Similarity	NPD7819	Suspended
0.6835	Remote Similarity	NPD1547	Clinical (unspecified phase)
0.6831	Remote Similarity	NPD5647	Approved
0.6828	Remote Similarity	NPD6663	Approved
0.6824	Remote Similarity	NPD3748	Approved
0.6812	Remote Similarity	NPD7163	Clinical (unspecified phase)
0.68	Remote Similarity	NPD4534	Discontinued
0.6794	Remote Similarity	NPD2182	Approved
0.679	Remote Similarity	NPD8127	Discontinued
0.6783	Remote Similarity	NPD5736	Approved
0.6781	Remote Similarity	NPD4060	Phase 1
0.6769	Remote Similarity	NPD3134	Approved
0.6765	Remote Similarity	NPD9493	Approved
0.6761	Remote Similarity	NPD3267	Approved
0.6761	Remote Similarity	NPD3266	Approved
0.6761	Remote Similarity	NPD1049	Clinical (unspecified phase)
0.6759	Remote Similarity	NPD6798	Discontinued
0.6755	Remote Similarity	NPD1243	Approved
0.6753	Remote Similarity	NPD2533	Approved
0.6753	Remote Similarity	NPD2532	Approved
0.6753	Remote Similarity	NPD2534	Approved
0.675	Remote Similarity	NPD7768	Phase 2
0.6736	Remote Similarity	NPD2614	Approved
0.6735	Remote Similarity	NPD447	Suspended
0.6735	Remote Similarity	NPD1899	Clinical (unspecified phase)
0.6732	Remote Similarity	NPD7440	Discontinued
0.6726	Remote Similarity	NPD6559	Discontinued
0.6713	Remote Similarity	NPD6007	Clinical (unspecified phase)
0.6713	Remote Similarity	NPD1019	Discontinued
0.6709	Remote Similarity	NPD7411	Suspended
0.6708	Remote Similarity	NPD3749	Approved
0.6691	Remote Similarity	NPD2932	Approved
0.669	Remote Similarity	NPD7095	Approved
0.6689	Remote Similarity	NPD5958	Discontinued
0.6689	Remote Similarity	NPD6653	Approved
0.6689	Remote Similarity	NPD970	Clinical (unspecified phase)
0.6667	Remote Similarity	NPD6099	Approved
0.6667	Remote Similarity	NPD2438	Suspended
0.6667	Remote Similarity	NPD9494	Approved
0.6667	Remote Similarity	NPD1481	Phase 2
0.6667	Remote Similarity	NPD6100	Approved
0.6667	Remote Similarity	NPD2531	Phase 2
0.6646	Remote Similarity	NPD7028	Phase 2
0.6645	Remote Similarity	NPD2800	Approved
0.6644	Remote Similarity	NPD6859	Clinical (unspecified phase)
0.6643	Remote Similarity	NPD6362	Approved
0.6625	Remote Similarity	NPD7096	Clinical (unspecified phase)
0.6623	Remote Similarity	NPD5763	Approved
0.6623	Remote Similarity	NPD7236	Approved
0.6623	Remote Similarity	NPD5762	Approved
0.6622	Remote Similarity	NPD4618	Approved
0.6622	Remote Similarity	NPD4622	Approved
0.662	Remote Similarity	NPD5327	Phase 3
0.6619	Remote Similarity	NPD1651	Approved
0.6618	Remote Similarity	NPD2629	Approved
0.6605	Remote Similarity	NPD7075	Discontinued
0.6601	Remote Similarity	NPD1878	Clinical (unspecified phase)
0.66	Remote Similarity	NPD7033	Discontinued
0.6599	Remote Similarity	NPD6233	Phase 2
0.6599	Remote Similarity	NPD4062	Phase 3
0.6599	Remote Similarity	NPD4870	Approved
0.6596	Remote Similarity	NPD1535	Discovery
0.6587	Remote Similarity	NPD7177	Discontinued
0.6581	Remote Similarity	NPD6799	Approved
0.6581	Remote Similarity	NPD6143	Clinical (unspecified phase)
0.6571	Remote Similarity	NPD3019	Approved
0.6569	Remote Similarity	NPD7157	Approved
0.6564	Remote Similarity	NPD919	Approved
0.6562	Remote Similarity	NPD1238	Approved
0.6561	Remote Similarity	NPD3873	Phase 3
0.6561	Remote Similarity	NPD3869	Phase 3
0.6561	Remote Similarity	NPD7427	Discontinued
0.6558	Remote Similarity	NPD3887	Approved
0.6558	Remote Similarity	NPD2354	Approved
0.6556	Remote Similarity	NPD2796	Approved
0.6554	Remote Similarity	NPD3142	Approved
0.6554	Remote Similarity	NPD3140	Approved
0.6548	Remote Similarity	NPD5844	Phase 1
0.6538	Remote Similarity	NPD4378	Clinical (unspecified phase)
0.6533	Remote Similarity	NPD5689	Approved
0.6533	Remote Similarity	NPD5688	Approved
0.6531	Remote Similarity	NPD1699	Clinical (unspecified phase)
0.6531	Remote Similarity	NPD6410	Clinical (unspecified phase)
0.6525	Remote Similarity	NPD3847	Discontinued
0.6525	Remote Similarity	NPD7457	Clinical (unspecified phase)
0.6519	Remote Similarity	NPD1609	Clinical (unspecified phase)
0.6513	Remote Similarity	NPD6800	Clinical (unspecified phase)
0.651	Remote Similarity	NPD1933	Approved
0.651	Remote Similarity	NPD5735	Approved
0.6503	Remote Similarity	NPD8005	Clinical (unspecified phase)
0.6497	Remote Similarity	NPD5049	Phase 3
0.6496	Remote Similarity	NPD690	Clinical (unspecified phase)
0.6489	Remote Similarity	NPD5909	Discontinued
0.6489	Remote Similarity	NPD164	Approved
0.6488	Remote Similarity	NPD7893	Clinical (unspecified phase)
0.6483	Remote Similarity	NPD6917	Clinical (unspecified phase)
0.6481	Remote Similarity	NPD8443	Clinical (unspecified phase)
0.6481	Remote Similarity	NPD2296	Approved
0.6479	Remote Similarity	NPD6287	Discontinued
0.6471	Remote Similarity	NPD5535	Approved
0.6471	Remote Similarity	NPD1549	Phase 2
0.6471	Remote Similarity	NPD2897	Discontinued
0.6467	Remote Similarity	NPD7852	Clinical (unspecified phase)
0.6467	Remote Similarity	NPD6353	Approved
0.6467	Remote Similarity	NPD1607	Approved
0.6467	Remote Similarity	NPD4575	Clinical (unspecified phase)
0.6467	Remote Similarity	NPD3451	Clinical (unspecified phase)
0.6466	Remote Similarity	NPD1358	Approved
0.646	Remote Similarity	NPD6279	Approved
0.646	Remote Similarity	NPD6280	Approved
0.646	Remote Similarity	NPD7577	Discontinued
0.646	Remote Similarity	NPD6801	Discontinued
0.6458	Remote Similarity	NPD6696	Suspended
0.6458	Remote Similarity	NPD3225	Approved
0.6456	Remote Similarity	NPD5403	Approved
0.6446	Remote Similarity	NPD6808	Phase 2
0.6443	Remote Similarity	NPD1240	Approved
0.6439	Remote Similarity	NPD9697	Approved
0.6438	Remote Similarity	NPD454	Approved
0.6433	Remote Similarity	NPD1578	Phase 2
0.6424	Remote Similarity	NPD7097	Phase 1
0.642	Remote Similarity	NPD1006	Clinical (unspecified phase)
0.6418	Remote Similarity	NPD2684	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