NPASS Compound

Structure

NPC306045 OpenBabel07101719512D 22 24 0 0 1 0 0 0 0 0999 V2000 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 -4.3301 -0.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4641 1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5981 -0.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7321 1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5981 -0.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1962 -0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3301 1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5981 1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4641 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 0 0 0 0 0 0 0 0 0 0 -3.4641 -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 0 0 0 0 0 0 0 0 0 0 -5.1962 1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4641 1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8660 -0.5000 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 0.8660 -0.5000 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -6.0622 1.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 4.3301 1.5000 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 2 1 0 0 0 0 1 3 2 0 0 0 0 2 18 1 0 0 0 0 3 19 1 0 0 0 0 4 9 1 0 0 0 0 4 14 2 0 0 0 0 5 10 2 0 0 0 0 5 14 1 0 0 0 0 6 13 1 0 0 0 0 6 14 1 0 0 0 0 7 11 1 0 0 0 0 7 15 2 0 0 0 0 8 12 2 0 0 0 0 8 15 1 0 0 0 0 9 16 2 0 0 0 0 10 16 1 0 0 0 0 11 17 2 0 0 0 0 12 17 1 0 0 0 0 16 20 1 0 0 0 0 17 21 1 0 0 0 0 18 13 1 6 0 0 0 18 22 1 0 0 0 0 19 15 1 1 0 0 0 19 22 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	296.14
Volume:	319.426
LogP:	3.924
LogD:	3.444
LogS:	-3.162
# Rotatable Bonds:	4
TPSA:	49.69
# H-Bond Aceptor:	3
# H-Bond Donor:	2
# Rings:	3
# Heavy Atoms:	3

MedChem Properties

QED Drug-Likeness Score:	0.835
Synthetic Accessibility Score:	3.223
Fsp3:	0.263
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected
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:	-4.625
MDCK Permeability:	1.3386867067310959e-05
Pgp-inhibitor:	0.002
Pgp-substrate:	0.003
Human Intestinal Absorption (HIA):	0.007
20% Bioavailability (F20%):	0.987
30% Bioavailability (F30%):	0.96

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.096
Plasma Protein Binding (PPB):	96.17418670654297%
Volume Distribution (VD):	1.03
Pgp-substrate:	3.5926125049591064%

ADMET: Metabolism

CYP1A2-inhibitor:	0.811
CYP1A2-substrate:	0.412
CYP2C19-inhibitor:	0.953
CYP2C19-substrate:	0.108
CYP2C9-inhibitor:	0.839
CYP2C9-substrate:	0.967
CYP2D6-inhibitor:	0.912
CYP2D6-substrate:	0.888
CYP3A4-inhibitor:	0.811
CYP3A4-substrate:	0.309

ADMET: Excretion

Clearance (CL):	12.407
Half-life (T1/2):	0.747

ADMET: Toxicity

hERG Blockers:	0.029
Human Hepatotoxicity (H-HT):	0.48
Drug-inuced Liver Injury (DILI):	0.025
AMES Toxicity:	0.365
Rat Oral Acute Toxicity:	0.212
Maximum Recommended Daily Dose:	0.908
Skin Sensitization:	0.927
Carcinogencity:	0.422
Eye Corrosion:	0.008
Eye Irritation:	0.691
Respiratory Toxicity:	0.411

Download Data

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

Natural Product: NPC306045

Natural Product ID:	NPC306045
*Common Name:**	(3S,7R)-5,6-Dehydro-1,7-Bis(4-Hydroxyphenyl)-De-Omethylcentrolobine
IUPAC Name:	4-[2-[(2S,6R)-6-(4-hydroxyphenyl)-3,6-dihydro-2H-pyran-2-yl]ethyl]phenol
Synonyms:
Standard InCHIKey:	WNMSDVNIAXMQRI-RTBURBONSA-N
Standard InCHI:	InChI=1S/C19H20O3/c20-16-9-4-14(5-10-16)6-13-18-2-1-3-19(22-18)15-7-11-17(21)12-8-15/h1,3-5,7-12,18-21H,2,6,13H2/t18-,19-/m1/s1
SMILES:	Oc1ccc(cc1)CC[C@H]1CC=C[C@@H](O1)c1ccc(cc1)O
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL478712
PubChem CID:	10780267
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0002650] Diarylheptanoids [CHEMONTID:0002651] Linear diarylheptanoids

*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
NPO6836	Alpinia blepharocalyx	Species	Zingiberaceae	Eukaryota	seeds	Mengha, Yunnan Province, China	1991-Aug	PMID[11277741]
NPO6836	Alpinia blepharocalyx	Species	Zingiberaceae	Eukaryota	seeds	n.a.	n.a.	PMID[11325233]
NPO6836	Alpinia blepharocalyx	Species	Zingiberaceae	Eukaryota	Seeds	n.a.	n.a.	PMID[11430002]
NPO6836	Alpinia blepharocalyx	Species	Zingiberaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[9461664]
NPO6836	Alpinia blepharocalyx	Species	Zingiberaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO6836	Alpinia blepharocalyx	Species	Zingiberaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO6836	Alpinia blepharocalyx	Species	Zingiberaceae	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
ED50	2

Activity Type	# Activity
Cell Line	1
NON-MOLECULAR	1

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT453	Cell Line	HT-1080	Homo sapiens	ED50	=	45.3	uM	PMID[475496]
NPT20529	NON-MOLECULAR	NON-PROTEIN TARGET	n.a.	ED50	=	71.2	uM	PMID[475496]

☑ 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 NPC306045 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	293
0.1-0.2	1476
0.2-0.3	4243
0.3-0.4	12643
0.4-0.5	6111
0.5-0.6	7300
0.6-0.7	7953
0.7-0.8	2481
0.8-0.85	158
0.85-0.9	30
0.9-0.95	7
0.95-1	2

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC265211
0.9524	High Similarity	NPC290353
0.9524	High Similarity	NPC153795
0.9524	High Similarity	NPC42911
0.9252	High Similarity	NPC123175
0.9252	High Similarity	NPC176730
0.9174	High Similarity	NPC473556
0.9174	High Similarity	NPC301651
0.9135	High Similarity	NPC135464
0.9135	High Similarity	NPC92623
0.9038	High Similarity	NPC154899
0.9038	High Similarity	NPC233396
0.8922	High Similarity	NPC51333
0.8922	High Similarity	NPC78119
0.8922	High Similarity	NPC216468
0.8922	High Similarity	NPC132078
0.8919	High Similarity	NPC476266
0.8835	High Similarity	NPC213730
0.8774	High Similarity	NPC113457
0.875	High Similarity	NPC7686
0.875	High Similarity	NPC91461
0.875	High Similarity	NPC40258
0.8713	High Similarity	NPC151715
0.8627	High Similarity	NPC26244
0.8621	High Similarity	NPC100099
0.8621	High Similarity	NPC174977
0.8621	High Similarity	NPC255026
0.8621	High Similarity	NPC36016
0.8596	High Similarity	NPC295259
0.8547	High Similarity	NPC76465
0.8547	High Similarity	NPC38761
0.8544	High Similarity	NPC473388
0.8534	High Similarity	NPC54972
0.8532	High Similarity	NPC474272
0.8522	High Similarity	NPC8283
0.8522	High Similarity	NPC258979
0.8522	High Similarity	NPC93398
0.8515	High Similarity	NPC45040
0.8509	High Similarity	NPC74821
0.8496	Intermediate Similarity	NPC54507
0.8496	Intermediate Similarity	NPC229147
0.8496	Intermediate Similarity	NPC85292
0.8476	Intermediate Similarity	NPC294741
0.8475	Intermediate Similarity	NPC197351
0.8475	Intermediate Similarity	NPC246648
0.8475	Intermediate Similarity	NPC106914
0.8475	Intermediate Similarity	NPC86502
0.8475	Intermediate Similarity	NPC134195
0.8462	Intermediate Similarity	NPC150026
0.8455	Intermediate Similarity	NPC475018
0.8455	Intermediate Similarity	NPC183700
0.8455	Intermediate Similarity	NPC63345
0.8448	Intermediate Similarity	NPC470414
0.8447	Intermediate Similarity	NPC313650
0.844	Intermediate Similarity	NPC201959
0.844	Intermediate Similarity	NPC75440
0.844	Intermediate Similarity	NPC206341
0.8421	Intermediate Similarity	NPC474933
0.8417	Intermediate Similarity	NPC149796
0.8407	Intermediate Similarity	NPC464
0.8407	Intermediate Similarity	NPC185541
0.8403	Intermediate Similarity	NPC102540
0.8403	Intermediate Similarity	NPC285040
0.8403	Intermediate Similarity	NPC188022
0.8403	Intermediate Similarity	NPC103420
0.8403	Intermediate Similarity	NPC17809
0.839	Intermediate Similarity	NPC473451
0.8365	Intermediate Similarity	NPC82664
0.8365	Intermediate Similarity	NPC132271
0.8365	Intermediate Similarity	NPC292730
0.8365	Intermediate Similarity	NPC216520
0.835	Intermediate Similarity	NPC128062
0.8349	Intermediate Similarity	NPC260952
0.8349	Intermediate Similarity	NPC251306
0.8348	Intermediate Similarity	NPC131118
0.8333	Intermediate Similarity	NPC276212
0.8333	Intermediate Similarity	NPC141090
0.8333	Intermediate Similarity	NPC474839
0.8333	Intermediate Similarity	NPC8302
0.8319	Intermediate Similarity	NPC257682
0.8319	Intermediate Similarity	NPC131747
0.8319	Intermediate Similarity	NPC146355
0.8318	Intermediate Similarity	NPC305205
0.8291	Intermediate Similarity	NPC469703
0.8291	Intermediate Similarity	NPC469704
0.8291	Intermediate Similarity	NPC160854
0.8291	Intermediate Similarity	NPC201402
0.8273	Intermediate Similarity	NPC262365
0.8269	Intermediate Similarity	NPC274678
0.8261	Intermediate Similarity	NPC122117
0.8252	Intermediate Similarity	NPC138117
0.8252	Intermediate Similarity	NPC325292
0.825	Intermediate Similarity	NPC81641
0.8246	Intermediate Similarity	NPC53906
0.8241	Intermediate Similarity	NPC119860
0.8235	Intermediate Similarity	NPC471693
0.8235	Intermediate Similarity	NPC300017
0.8235	Intermediate Similarity	NPC300478
0.823	Intermediate Similarity	NPC35344
0.823	Intermediate Similarity	NPC141003
0.822	Intermediate Similarity	NPC469686
0.822	Intermediate Similarity	NPC193364
0.8208	Intermediate Similarity	NPC92730
0.8198	Intermediate Similarity	NPC62258
0.8198	Intermediate Similarity	NPC55617
0.8197	Intermediate Similarity	NPC87224
0.8197	Intermediate Similarity	NPC148366
0.8197	Intermediate Similarity	NPC471064
0.8197	Intermediate Similarity	NPC311293
0.8197	Intermediate Similarity	NPC274717
0.8197	Intermediate Similarity	NPC474178
0.8197	Intermediate Similarity	NPC252307
0.8197	Intermediate Similarity	NPC245826
0.8197	Intermediate Similarity	NPC222572
0.8182	Intermediate Similarity	NPC283049
0.8182	Intermediate Similarity	NPC50315
0.8182	Intermediate Similarity	NPC230479
0.8182	Intermediate Similarity	NPC26879
0.8174	Intermediate Similarity	NPC175771
0.8173	Intermediate Similarity	NPC76938
0.8165	Intermediate Similarity	NPC470393
0.8158	Intermediate Similarity	NPC473137
0.8158	Intermediate Similarity	NPC180508
0.8158	Intermediate Similarity	NPC228287
0.8158	Intermediate Similarity	NPC161696
0.8158	Intermediate Similarity	NPC22610
0.8158	Intermediate Similarity	NPC276737
0.8158	Intermediate Similarity	NPC12656
0.8158	Intermediate Similarity	NPC120280
0.8151	Intermediate Similarity	NPC471067
0.8148	Intermediate Similarity	NPC62351
0.8148	Intermediate Similarity	NPC168829
0.8148	Intermediate Similarity	NPC135784
0.8137	Intermediate Similarity	NPC242240
0.8137	Intermediate Similarity	NPC123273
0.8137	Intermediate Similarity	NPC318325
0.8137	Intermediate Similarity	NPC177420
0.8137	Intermediate Similarity	NPC280347
0.813	Intermediate Similarity	NPC134360
0.8125	Intermediate Similarity	NPC321252
0.8125	Intermediate Similarity	NPC120982
0.8125	Intermediate Similarity	NPC147634
0.8125	Intermediate Similarity	NPC79793
0.8125	Intermediate Similarity	NPC226401
0.8125	Intermediate Similarity	NPC44732
0.8125	Intermediate Similarity	NPC252544
0.8125	Intermediate Similarity	NPC174096
0.812	Intermediate Similarity	NPC59561
0.812	Intermediate Similarity	NPC121866
0.812	Intermediate Similarity	NPC172253
0.8113	Intermediate Similarity	NPC225464
0.8108	Intermediate Similarity	NPC61885
0.8108	Intermediate Similarity	NPC63698
0.8103	Intermediate Similarity	NPC15860
0.8103	Intermediate Similarity	NPC33270
0.8103	Intermediate Similarity	NPC195466
0.8103	Intermediate Similarity	NPC219070
0.8103	Intermediate Similarity	NPC470759
0.8103	Intermediate Similarity	NPC69261
0.8103	Intermediate Similarity	NPC127894
0.8099	Intermediate Similarity	NPC124030
0.8099	Intermediate Similarity	NPC278552
0.8099	Intermediate Similarity	NPC148627
0.8099	Intermediate Similarity	NPC194519
0.8099	Intermediate Similarity	NPC207179
0.8099	Intermediate Similarity	NPC167571
0.8095	Intermediate Similarity	NPC32714
0.8087	Intermediate Similarity	NPC232165
0.8083	Intermediate Similarity	NPC178449
0.8083	Intermediate Similarity	NPC470907
0.8083	Intermediate Similarity	NPC232454
0.8083	Intermediate Similarity	NPC474160
0.8073	Intermediate Similarity	NPC261573
0.8073	Intermediate Similarity	NPC241891
0.8073	Intermediate Similarity	NPC120693
0.8073	Intermediate Similarity	NPC108875
0.8073	Intermediate Similarity	NPC323810
0.8073	Intermediate Similarity	NPC12987
0.8073	Intermediate Similarity	NPC474603
0.8073	Intermediate Similarity	NPC8931
0.8073	Intermediate Similarity	NPC288411
0.8073	Intermediate Similarity	NPC30506
0.8073	Intermediate Similarity	NPC38079
0.8067	Intermediate Similarity	NPC147654
0.8067	Intermediate Similarity	NPC476633
0.8067	Intermediate Similarity	NPC290451
0.8067	Intermediate Similarity	NPC127389
0.8058	Intermediate Similarity	NPC55561
0.8053	Intermediate Similarity	NPC266932
0.8053	Intermediate Similarity	NPC139946
0.8053	Intermediate Similarity	NPC177576
0.8053	Intermediate Similarity	NPC179002
0.8053	Intermediate Similarity	NPC187583
0.8053	Intermediate Similarity	NPC257430
0.8053	Intermediate Similarity	NPC308689
0.8051	Intermediate Similarity	NPC282255
0.8049	Intermediate Similarity	NPC47283
0.8049	Intermediate Similarity	NPC129570
0.8049	Intermediate Similarity	NPC72529
0.8049	Intermediate Similarity	NPC45774

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 NPC306045 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	284
0.1-0.2	922
0.2-0.3	1325
0.3-0.4	2751
0.4-0.5	1965
0.5-0.6	1145
0.6-0.7	656
0.7-0.8	92
0.8-0.85	8
0.85-0.9	2
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.8627	High Similarity	NPD2860	Approved
0.8627	High Similarity	NPD2859	Approved
0.8529	High Similarity	NPD2934	Approved
0.8529	High Similarity	NPD2933	Approved
0.8509	High Similarity	NPD1548	Phase 1
0.8381	Intermediate Similarity	NPD3020	Approved
0.8264	Intermediate Similarity	NPD2861	Phase 2
0.822	Intermediate Similarity	NPD1610	Phase 2
0.8091	Intermediate Similarity	NPD968	Approved
0.8049	Intermediate Similarity	NPD4908	Phase 1
0.7946	Intermediate Similarity	NPD2684	Approved
0.7934	Intermediate Similarity	NPD6582	Phase 2
0.7934	Intermediate Similarity	NPD6583	Phase 3
0.792	Intermediate Similarity	NPD4907	Clinical (unspecified phase)
0.7899	Intermediate Similarity	NPD5238	Clinical (unspecified phase)
0.789	Intermediate Similarity	NPD940	Approved
0.789	Intermediate Similarity	NPD846	Approved
0.7876	Intermediate Similarity	NPD5451	Approved
0.784	Intermediate Similarity	NPD3027	Phase 3
0.783	Intermediate Similarity	NPD1432	Clinical (unspecified phase)
0.7798	Intermediate Similarity	NPD1242	Phase 1
0.775	Intermediate Similarity	NPD6516	Phase 2
0.775	Intermediate Similarity	NPD5846	Approved
0.7742	Intermediate Similarity	NPD6584	Phase 3
0.7719	Intermediate Similarity	NPD3021	Approved
0.7719	Intermediate Similarity	NPD3022	Approved
0.7672	Intermediate Similarity	NPD5535	Approved
0.7672	Intermediate Similarity	NPD7843	Approved
0.7656	Intermediate Similarity	NPD1613	Approved
0.7656	Intermediate Similarity	NPD1612	Clinical (unspecified phase)
0.7647	Intermediate Similarity	NPD111	Approved
0.7642	Intermediate Similarity	NPD4659	Approved
0.7583	Intermediate Similarity	NPD9545	Approved
0.7583	Intermediate Similarity	NPD3091	Approved
0.7576	Intermediate Similarity	NPD2029	Clinical (unspecified phase)
0.7565	Intermediate Similarity	NPD9380	Clinical (unspecified phase)
0.7521	Intermediate Similarity	NPD821	Approved
0.752	Intermediate Similarity	NPD4104	Clinical (unspecified phase)
0.752	Intermediate Similarity	NPD4103	Phase 2
0.75	Intermediate Similarity	NPD3764	Approved
0.75	Intermediate Similarity	NPD3600	Clinical (unspecified phase)
0.7481	Intermediate Similarity	NPD4978	Clinical (unspecified phase)
0.748	Intermediate Similarity	NPD1529	Clinical (unspecified phase)
0.748	Intermediate Similarity	NPD422	Phase 1
0.748	Intermediate Similarity	NPD3092	Approved
0.7479	Intermediate Similarity	NPD7157	Approved
0.7479	Intermediate Similarity	NPD6671	Approved
0.7477	Intermediate Similarity	NPD3028	Approved
0.7462	Intermediate Similarity	NPD4340	Discontinued
0.7458	Intermediate Similarity	NPD5283	Phase 1
0.7438	Intermediate Similarity	NPD6581	Approved
0.7438	Intermediate Similarity	NPD1894	Discontinued
0.7438	Intermediate Similarity	NPD6580	Approved
0.7436	Intermediate Similarity	NPD228	Approved
0.7431	Intermediate Similarity	NPD1809	Phase 2
0.7431	Intermediate Similarity	NPD844	Approved
0.7424	Intermediate Similarity	NPD7033	Discontinued
0.7422	Intermediate Similarity	NPD4625	Phase 3
0.7419	Intermediate Similarity	NPD2562	Approved
0.7419	Intermediate Similarity	NPD2561	Approved
0.7417	Intermediate Similarity	NPD3596	Phase 2
0.7407	Intermediate Similarity	NPD845	Approved
0.7405	Intermediate Similarity	NPD3052	Approved
0.7405	Intermediate Similarity	NPD3054	Approved
0.7402	Intermediate Similarity	NPD1530	Clinical (unspecified phase)
0.7398	Intermediate Similarity	NPD3847	Discontinued
0.7391	Intermediate Similarity	NPD290	Approved
0.7377	Intermediate Similarity	NPD6830	Clinical (unspecified phase)
0.7372	Intermediate Similarity	NPD7213	Phase 3
0.7372	Intermediate Similarity	NPD7212	Phase 2
0.7364	Intermediate Similarity	NPD6798	Discontinued
0.7364	Intermediate Similarity	NPD6859	Clinical (unspecified phase)
0.736	Intermediate Similarity	NPD4749	Approved
0.7348	Intermediate Similarity	NPD4536	Approved
0.7348	Intermediate Similarity	NPD4537	Clinical (unspecified phase)
0.7348	Intermediate Similarity	NPD4538	Approved
0.7339	Intermediate Similarity	NPD1091	Approved
0.7317	Intermediate Similarity	NPD2667	Approved
0.7317	Intermediate Similarity	NPD2668	Approved
0.7313	Intermediate Similarity	NPD1550	Clinical (unspecified phase)
0.7313	Intermediate Similarity	NPD7266	Discontinued
0.7313	Intermediate Similarity	NPD1552	Clinical (unspecified phase)
0.7311	Intermediate Similarity	NPD2228	Approved
0.7311	Intermediate Similarity	NPD2234	Approved
0.7311	Intermediate Similarity	NPD2229	Approved
0.7308	Intermediate Similarity	NPD6407	Approved
0.7308	Intermediate Similarity	NPD6405	Approved
0.7304	Intermediate Similarity	NPD3134	Approved
0.7302	Intermediate Similarity	NPD7258	Clinical (unspecified phase)
0.7302	Intermediate Similarity	NPD8651	Approved
0.7295	Intermediate Similarity	NPD7741	Discontinued
0.7293	Intermediate Similarity	NPD5588	Approved
0.7293	Intermediate Similarity	NPD5960	Phase 3
0.7293	Intermediate Similarity	NPD1510	Phase 2
0.728	Intermediate Similarity	NPD2235	Phase 2
0.728	Intermediate Similarity	NPD2231	Phase 2
0.7266	Intermediate Similarity	NPD5736	Approved
0.7265	Intermediate Similarity	NPD4750	Phase 3
0.7259	Intermediate Similarity	NPD1549	Phase 2
0.7252	Intermediate Similarity	NPD5837	Clinical (unspecified phase)
0.7252	Intermediate Similarity	NPD4060	Phase 1
0.7244	Intermediate Similarity	NPD3094	Phase 2
0.7244	Intermediate Similarity	NPD2797	Approved
0.7241	Intermediate Similarity	NPD2342	Discontinued
0.7231	Intermediate Similarity	NPD6410	Clinical (unspecified phase)
0.7222	Intermediate Similarity	NPD3685	Discontinued
0.7222	Intermediate Similarity	NPD5327	Phase 3
0.7213	Intermediate Similarity	NPD16	Approved
0.7213	Intermediate Similarity	NPD856	Approved
0.7207	Intermediate Similarity	NPD288	Approved
0.7206	Intermediate Similarity	NPD5698	Clinical (unspecified phase)
0.7206	Intermediate Similarity	NPD7421	Clinical (unspecified phase)
0.72	Intermediate Similarity	NPD1535	Discovery
0.7197	Intermediate Similarity	NPD5123	Clinical (unspecified phase)
0.7197	Intermediate Similarity	NPD5124	Phase 1
0.7197	Intermediate Similarity	NPD5735	Approved
0.7194	Intermediate Similarity	NPD7447	Phase 1
0.719	Intermediate Similarity	NPD2557	Approved
0.7177	Intermediate Similarity	NPD3095	Discontinued
0.7177	Intermediate Similarity	NPD5125	Phase 3
0.7177	Intermediate Similarity	NPD5126	Approved
0.7176	Intermediate Similarity	NPD6233	Phase 2
0.7168	Intermediate Similarity	NPD2553	Approved
0.7168	Intermediate Similarity	NPD2549	Approved
0.7168	Intermediate Similarity	NPD2550	Approved
0.7168	Intermediate Similarity	NPD2555	Approved
0.7168	Intermediate Similarity	NPD2552	Approved
0.7168	Intermediate Similarity	NPD289	Clinical (unspecified phase)
0.7168	Intermediate Similarity	NPD2558	Approved
0.7167	Intermediate Similarity	NPD7159	Clinical (unspecified phase)
0.7165	Intermediate Similarity	NPD3225	Approved
0.7154	Intermediate Similarity	NPD6179	Discontinued
0.7153	Intermediate Similarity	NPD4628	Phase 3
0.7143	Intermediate Similarity	NPD1481	Phase 2
0.7143	Intermediate Similarity	NPD6124	Clinical (unspecified phase)
0.7143	Intermediate Similarity	NPD1608	Approved
0.7132	Intermediate Similarity	NPD4993	Discontinued
0.7121	Intermediate Similarity	NPD3620	Phase 2
0.7121	Intermediate Similarity	NPD1240	Approved
0.7121	Intermediate Similarity	NPD2238	Phase 2
0.7121	Intermediate Similarity	NPD3619	Clinical (unspecified phase)
0.7121	Intermediate Similarity	NPD4140	Approved
0.7111	Intermediate Similarity	NPD2796	Approved
0.7109	Intermediate Similarity	NPD4339	Clinical (unspecified phase)
0.7107	Intermediate Similarity	NPD1476	Clinical (unspecified phase)
0.7105	Intermediate Similarity	NPD4189	Approved
0.7105	Intermediate Similarity	NPD4188	Approved
0.7097	Intermediate Similarity	NPD4093	Discontinued
0.7094	Intermediate Similarity	NPD1358	Approved
0.7087	Intermediate Similarity	NPD6540	Phase 3
0.7087	Intermediate Similarity	NPD6542	Approved
0.7087	Intermediate Similarity	NPD6539	Approved
0.7087	Intermediate Similarity	NPD4379	Clinical (unspecified phase)
0.7087	Intermediate Similarity	NPD6543	Approved
0.7083	Intermediate Similarity	NPD7635	Approved
0.7073	Intermediate Similarity	NPD318	Approved
0.7073	Intermediate Similarity	NPD317	Approved
0.7071	Intermediate Similarity	NPD4378	Clinical (unspecified phase)
0.7071	Intermediate Similarity	NPD4160	Clinical (unspecified phase)
0.7068	Intermediate Similarity	NPD6355	Discontinued
0.7063	Intermediate Similarity	NPD5350	Clinical (unspecified phase)
0.7063	Intermediate Similarity	NPD5351	Clinical (unspecified phase)
0.7063	Intermediate Similarity	NPD4380	Phase 2
0.7054	Intermediate Similarity	NPD4624	Approved
0.7054	Intermediate Similarity	NPD6917	Clinical (unspecified phase)
0.705	Intermediate Similarity	NPD6815	Approved
0.705	Intermediate Similarity	NPD5058	Phase 3
0.7045	Intermediate Similarity	NPD4062	Phase 3
0.7045	Intermediate Similarity	NPD6663	Approved
0.704	Intermediate Similarity	NPD4059	Approved
0.704	Intermediate Similarity	NPD4626	Approved
0.704	Intermediate Similarity	NPD2286	Discontinued
0.704	Intermediate Similarity	NPD2932	Approved
0.704	Intermediate Similarity	NPD3019	Approved
0.7037	Intermediate Similarity	NPD3846	Clinical (unspecified phase)
0.7031	Intermediate Similarity	NPD6538	Approved
0.7031	Intermediate Similarity	NPD6541	Approved
0.7029	Intermediate Similarity	NPD3750	Approved
0.7025	Intermediate Similarity	NPD1241	Discontinued
0.7023	Intermediate Similarity	NPD7095	Approved
0.7023	Intermediate Similarity	NPD5163	Phase 2
0.7016	Intermediate Similarity	NPD1182	Approved
0.7016	Intermediate Similarity	NPD5303	Approved
0.7016	Intermediate Similarity	NPD5304	Approved
0.7015	Intermediate Similarity	NPD1607	Approved
0.7015	Intermediate Similarity	NPD6353	Approved
0.7009	Intermediate Similarity	NPD3526	Approved
0.7009	Intermediate Similarity	NPD3524	Approved
0.7008	Intermediate Similarity	NPD2232	Approved
0.7008	Intermediate Similarity	NPD2230	Approved
0.7008	Intermediate Similarity	NPD2233	Approved
0.7007	Intermediate Similarity	NPD7037	Approved
0.6992	Remote Similarity	NPD1558	Phase 1
0.6984	Remote Similarity	NPD3421	Phase 3
0.6983	Remote Similarity	NPD9608	Approved
0.6983	Remote Similarity	NPD3047	Approved
0.6983	Remote Similarity	NPD3046	Approved
0.6983	Remote Similarity	NPD3048	Approved
0.6983	Remote Similarity	NPD9610	Approved
0.6978	Remote Similarity	NPD6190	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