NPASS Compound

Structure

NPC476434 OpenBabel07101719252D 32 35 0 0 1 0 0 0 0 0999 V2000 6.2788 -1.2024 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8147 -0.2024 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9013 -1.8841 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6808 0.2976 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8958 -1.9886 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9487 -1.7024 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6808 -1.7024 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9898 -2.8963 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7044 -3.2564 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0823 -0.1615 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4546 -4.5436 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8147 -1.2024 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4945 -0.9706 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0388 -2.5873 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1977 -3.8745 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4965 -4.2346 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0827 -1.2024 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4836 -1.1796 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5468 -0.2024 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0768 -0.2661 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5468 -1.2024 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1691 -1.6092 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.5000 -0.8660 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 0.9781 -0.2079 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1488 -4.1835 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.2396 -4.9037 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.4781 -1.2841 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 5.4128 0.2976 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.6646 0.5430 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.7213 0.4612 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 5.4128 -1.7024 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 31 1 0 0 0 0 2 4 2 0 0 0 0 2 12 1 0 0 0 0 3 5 2 0 0 0 0 3 13 1 0 0 0 0 4 19 1 0 0 0 0 5 18 1 0 0 0 0 6 12 1 0 0 0 0 6 17 2 0 0 0 0 7 12 2 0 0 0 0 7 21 1 0 0 0 0 8 14 2 0 0 0 0 8 15 1 0 0 0 0 9 14 1 0 0 0 0 9 16 2 0 0 0 0 10 13 2 0 0 0 0 10 20 1 0 0 0 0 11 15 2 0 0 0 0 11 16 1 0 0 0 0 15 25 1 0 0 0 0 16 26 1 0 0 0 0 17 22 1 0 0 0 0 17 24 1 0 0 0 0 18 20 2 0 0 0 0 18 27 1 0 0 0 0 19 21 2 0 0 0 0 19 28 1 0 0 0 0 20 29 1 0 0 0 0 21 31 1 0 0 0 0 22 14 1 6 0 0 0 22 23 1 0 0 0 0 23 13 1 1 0 0 0 23 32 1 0 0 0 0 24 30 2 0 0 0 0 24 32 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	436.12
Volume:	430.755
LogP:	3.128
LogD:	2.786
LogS:	-3.651
# Rotatable Bonds:	4
TPSA:	136.68
# H-Bond Aceptor:	8
# H-Bond Donor:	5
# Rings:	4
# Heavy Atoms:	8

MedChem Properties

QED Drug-Likeness Score:	0.237
Synthetic Accessibility Score:	3.574
Fsp3:	0.125
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Accepted
GSK Rule:	Rejected
BMS Rule:	1
Golden Triangle Rule:	Accepted
Chelating Alert:	2
PAINS Alert:	1

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-5.339
MDCK Permeability:	1.2248590792296454e-05
Pgp-inhibitor:	0.074
Pgp-substrate:	0.032
Human Intestinal Absorption (HIA):	0.022
20% Bioavailability (F20%):	0.76
30% Bioavailability (F30%):	0.988

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.012
Plasma Protein Binding (PPB):	95.84844970703125%
Volume Distribution (VD):	0.596
Pgp-substrate:	4.485490322113037%

ADMET: Metabolism

CYP1A2-inhibitor:	0.854
CYP1A2-substrate:	0.659
CYP2C19-inhibitor:	0.324
CYP2C19-substrate:	0.047
CYP2C9-inhibitor:	0.696
CYP2C9-substrate:	0.935
CYP2D6-inhibitor:	0.358
CYP2D6-substrate:	0.499
CYP3A4-inhibitor:	0.805
CYP3A4-substrate:	0.167

ADMET: Excretion

Clearance (CL):	15.511
Half-life (T1/2):	0.868

ADMET: Toxicity

hERG Blockers:	0.062
Human Hepatotoxicity (H-HT):	0.252
Drug-inuced Liver Injury (DILI):	0.817
AMES Toxicity:	0.096
Rat Oral Acute Toxicity:	0.521
Maximum Recommended Daily Dose:	0.942
Skin Sensitization:	0.956
Carcinogencity:	0.135
Eye Corrosion:	0.004
Eye Irritation:	0.898
Respiratory Toxicity:	0.68

Download Data

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

Natural Product: NPC476434

Natural Product ID:	NPC476434
*Common Name:**	Jezonolide
IUPAC Name:	(3E,4S,5S)-5-(3,4-dihydroxyphenyl)-4-(3,5-dihydroxyphenyl)-3-[(4-hydroxy-3-methoxyphenyl)methylidene]oxolan-2-one
Synonyms:	Jezonolide
Standard InCHIKey:	IBZKQAXTWQRPIW-IJBCTFMISA-N
Standard InCHI:	InChI=1S/C24H20O8/c1-31-21-7-12(2-4-19(21)28)6-17-22(14-8-15(25)11-16(26)9-14)23(32-24(17)30)13-3-5-18(27)20(29)10-13/h2-11,22-23,25-29H,1H3/b17-6+/t22-,23+/m0/s1
SMILES:	COC1=C(C=CC(=C1)C=C2C(C(OC2=O)C3=CC(=C(C=C3)O)O)C4=CC(=CC(=C4)O)O)O
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL604877
PubChem CID:	46226509
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000253] Stilbenes

*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
NPO6645.1	Picea jezoensis var. jezoensis	Varieties	Pinaceae	Eukaryota	bark	n.a.	n.a.	PMID[17907781]
NPO6645.1	Picea jezoensis var. jezoensis	Varieties	Pinaceae	Eukaryota	bark	n.a.	n.a.	PMID[19646881]
NPO6645.1	Picea jezoensis var. jezoensis	Varieties	Pinaceae	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
Others	1

Activity Type	# Activity
NON-MOLECULAR	1

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT20529	NON-MOLECULAR	NON-PROTEIN TARGET	n.a.	Ratio	=	2.1	n.a.	PMID[542416]

☑ 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 NPC476434 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	330
0.1-0.2	1294
0.2-0.3	2958
0.3-0.4	7011
0.4-0.5	10932
0.5-0.6	4538
0.6-0.7	6008
0.7-0.8	8210
0.8-0.85	1177
0.85-0.9	219
0.9-0.95	17
0.95-1	3

Similarity Score	Similarity Level	Natural Product ID
0.9452	High Similarity	NPC102934
0.9452	High Similarity	NPC252402
0.9375	High Similarity	NPC477696
0.9375	High Similarity	NPC477697
0.9375	High Similarity	NPC470811
0.9375	High Similarity	NPC273657
0.9375	High Similarity	NPC106920
0.9329	High Similarity	NPC267091
0.9306	High Similarity	NPC67467
0.9267	High Similarity	NPC178574
0.9267	High Similarity	NPC65591
0.9262	High Similarity	NPC243891
0.9257	High Similarity	NPC125570
0.9139	High Similarity	NPC473236
0.9133	High Similarity	NPC477700
0.9133	High Similarity	NPC32079
0.9103	High Similarity	NPC100675
0.9073	High Similarity	NPC93498
0.9073	High Similarity	NPC163883
0.9073	High Similarity	NPC246566
0.9073	High Similarity	NPC95498
0.9051	High Similarity	NPC311912
0.9038	High Similarity	NPC42797
0.9038	High Similarity	NPC473445
0.9032	High Similarity	NPC53889
0.902	High Similarity	NPC203757
0.9013	High Similarity	NPC19380
0.9013	High Similarity	NPC146277
0.9	High Similarity	NPC668
0.9	High Similarity	NPC474965
0.9	High Similarity	NPC477695
0.9	High Similarity	NPC216223
0.9	High Similarity	NPC293757
0.9	High Similarity	NPC174512
0.9	High Similarity	NPC145569
0.8994	High Similarity	NPC88557
0.8986	High Similarity	NPC223185
0.8981	High Similarity	NPC291977
0.8968	High Similarity	NPC87317
0.8958	High Similarity	NPC90431
0.8954	High Similarity	NPC25127
0.8954	High Similarity	NPC136757
0.8954	High Similarity	NPC287504
0.8947	High Similarity	NPC75695
0.8947	High Similarity	NPC477699
0.8938	High Similarity	NPC180768
0.8919	High Similarity	NPC27159
0.8912	High Similarity	NPC31751
0.8912	High Similarity	NPC253481
0.8912	High Similarity	NPC253722
0.891	High Similarity	NPC91634
0.891	High Similarity	NPC268718
0.891	High Similarity	NPC150943
0.8903	High Similarity	NPC289322
0.8903	High Similarity	NPC114179
0.8903	High Similarity	NPC125495
0.8903	High Similarity	NPC156818
0.8903	High Similarity	NPC160512
0.8903	High Similarity	NPC68324
0.8903	High Similarity	NPC38779
0.8897	High Similarity	NPC281780
0.8896	High Similarity	NPC476642
0.8896	High Similarity	NPC145425
0.8889	High Similarity	NPC475141
0.8889	High Similarity	NPC474656
0.8889	High Similarity	NPC72796
0.8889	High Similarity	NPC211386
0.8889	High Similarity	NPC44245
0.8868	High Similarity	NPC43065
0.8861	High Similarity	NPC272750
0.8861	High Similarity	NPC223006
0.8861	High Similarity	NPC134047
0.8861	High Similarity	NPC173729
0.8854	High Similarity	NPC216916
0.8854	High Similarity	NPC469889
0.8846	High Similarity	NPC230531
0.8846	High Similarity	NPC215400
0.8844	High Similarity	NPC470991
0.8839	High Similarity	NPC104983
0.8839	High Similarity	NPC165483
0.8839	High Similarity	NPC291948
0.8839	High Similarity	NPC88803
0.8839	High Similarity	NPC300845
0.8839	High Similarity	NPC250436
0.8831	High Similarity	NPC473736
0.8831	High Similarity	NPC30009
0.8831	High Similarity	NPC103197
0.8828	High Similarity	NPC471988
0.8824	High Similarity	NPC151425
0.8824	High Similarity	NPC56184
0.8819	High Similarity	NPC300776
0.8819	High Similarity	NPC67247
0.8819	High Similarity	NPC68779
0.8819	High Similarity	NPC176814
0.8819	High Similarity	NPC4982
0.8819	High Similarity	NPC5310
0.8816	High Similarity	NPC473091
0.8808	High Similarity	NPC1580
0.88	High Similarity	NPC40222
0.88	High Similarity	NPC268515
0.8797	High Similarity	NPC144557
0.8792	High Similarity	NPC160378
0.879	High Similarity	NPC24627
0.879	High Similarity	NPC24164
0.879	High Similarity	NPC301089
0.879	High Similarity	NPC476373
0.8782	High Similarity	NPC163527
0.8782	High Similarity	NPC181168
0.8782	High Similarity	NPC472860
0.8782	High Similarity	NPC115281
0.8782	High Similarity	NPC143328
0.8776	High Similarity	NPC147379
0.8776	High Similarity	NPC288452
0.8776	High Similarity	NPC289690
0.8766	High Similarity	NPC115466
0.8766	High Similarity	NPC44730
0.8766	High Similarity	NPC61604
0.8766	High Similarity	NPC245948
0.8766	High Similarity	NPC245615
0.8766	High Similarity	NPC299706
0.8766	High Similarity	NPC470769
0.8759	High Similarity	NPC113295
0.8758	High Similarity	NPC300329
0.8758	High Similarity	NPC62354
0.875	High Similarity	NPC475250
0.875	High Similarity	NPC83049
0.875	High Similarity	NPC158331
0.875	High Similarity	NPC474393
0.875	High Similarity	NPC320471
0.875	High Similarity	NPC474347
0.875	High Similarity	NPC118162
0.8742	High Similarity	NPC116759
0.8742	High Similarity	NPC45943
0.8742	High Similarity	NPC14294
0.8742	High Similarity	NPC299090
0.8742	High Similarity	NPC283081
0.8742	High Similarity	NPC143892
0.8742	High Similarity	NPC30720
0.8742	High Similarity	NPC221383
0.8734	High Similarity	NPC109061
0.8733	High Similarity	NPC477702
0.8718	High Similarity	NPC470896
0.8718	High Similarity	NPC473275
0.8718	High Similarity	NPC237946
0.8718	High Similarity	NPC32373
0.8718	High Similarity	NPC318432
0.8716	High Similarity	NPC9218
0.8716	High Similarity	NPC29599
0.8701	High Similarity	NPC478268
0.8699	High Similarity	NPC120852
0.8696	High Similarity	NPC79322
0.8696	High Similarity	NPC215802
0.8696	High Similarity	NPC167231
0.8693	High Similarity	NPC470916
0.8693	High Similarity	NPC221091
0.8693	High Similarity	NPC259576
0.869	High Similarity	NPC135127
0.869	High Similarity	NPC287745
0.869	High Similarity	NPC244983
0.869	High Similarity	NPC326095
0.8688	High Similarity	NPC475738
0.8688	High Similarity	NPC142614
0.8688	High Similarity	NPC471788
0.8684	High Similarity	NPC139839
0.8684	High Similarity	NPC236166
0.8684	High Similarity	NPC472969
0.8681	High Similarity	NPC204215
0.8681	High Similarity	NPC175067
0.8679	High Similarity	NPC33298
0.8679	High Similarity	NPC76687
0.8679	High Similarity	NPC476372
0.8679	High Similarity	NPC249070
0.8679	High Similarity	NPC285108
0.8679	High Similarity	NPC476371
0.8675	High Similarity	NPC98356
0.8675	High Similarity	NPC212890
0.8671	High Similarity	NPC203020
0.8671	High Similarity	NPC239966
0.8667	High Similarity	NPC475000
0.8667	High Similarity	NPC470097
0.8667	High Similarity	NPC114119
0.8667	High Similarity	NPC471415
0.8667	High Similarity	NPC16353
0.8662	High Similarity	NPC207584
0.8662	High Similarity	NPC35598
0.8662	High Similarity	NPC19947
0.8662	High Similarity	NPC222689
0.8658	High Similarity	NPC46180
0.8658	High Similarity	NPC52664
0.8654	High Similarity	NPC238834
0.8654	High Similarity	NPC476065
0.8654	High Similarity	NPC38699
0.8649	High Similarity	NPC266197
0.8649	High Similarity	NPC291101
0.8645	High Similarity	NPC115203
0.8642	High Similarity	NPC476279
0.8642	High Similarity	NPC117911
0.863	High Similarity	NPC126409
0.863	High Similarity	NPC34103
0.863	High Similarity	NPC24490

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 NPC476434 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	285
0.1-0.2	796
0.2-0.3	1596
0.3-0.4	2540
0.4-0.5	2111
0.5-0.6	1099
0.6-0.7	560
0.7-0.8	141
0.8-0.85	17
0.85-0.9	5
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.8968	High Similarity	NPD6234	Discontinued
0.8839	High Similarity	NPD4868	Clinical (unspecified phase)
0.8766	High Similarity	NPD37	Approved
0.8718	High Similarity	NPD4967	Phase 2
0.8718	High Similarity	NPD4965	Approved
0.8718	High Similarity	NPD4966	Approved
0.858	High Similarity	NPD7228	Approved
0.8442	Intermediate Similarity	NPD6980	Clinical (unspecified phase)
0.8385	Intermediate Similarity	NPD7199	Phase 2
0.8366	Intermediate Similarity	NPD6143	Clinical (unspecified phase)
0.8355	Intermediate Similarity	NPD6190	Approved
0.8354	Intermediate Similarity	NPD3818	Discontinued
0.8345	Intermediate Similarity	NPD3027	Phase 3
0.8333	Intermediate Similarity	NPD6232	Discontinued
0.8293	Intermediate Similarity	NPD7473	Discontinued
0.8291	Intermediate Similarity	NPD1934	Approved
0.8284	Intermediate Similarity	NPD8055	Clinical (unspecified phase)
0.8282	Intermediate Similarity	NPD7184	Clinical (unspecified phase)
0.825	Intermediate Similarity	NPD3882	Suspended
0.8232	Intermediate Similarity	NPD6167	Clinical (unspecified phase)
0.8232	Intermediate Similarity	NPD6168	Clinical (unspecified phase)
0.8232	Intermediate Similarity	NPD6166	Phase 2
0.8204	Intermediate Similarity	NPD7993	Clinical (unspecified phase)
0.8193	Intermediate Similarity	NPD5844	Phase 1
0.8125	Intermediate Similarity	NPD2393	Clinical (unspecified phase)
0.8125	Intermediate Similarity	NPD1465	Phase 2
0.8125	Intermediate Similarity	NPD2801	Approved
0.8121	Intermediate Similarity	NPD230	Phase 1
0.8075	Intermediate Similarity	NPD3817	Phase 2
0.8047	Intermediate Similarity	NPD7240	Approved
0.7988	Intermediate Similarity	NPD5494	Approved
0.7941	Intermediate Similarity	NPD7685	Pre-registration
0.7933	Intermediate Similarity	NPD1612	Clinical (unspecified phase)
0.7933	Intermediate Similarity	NPD1613	Approved
0.7929	Intermediate Similarity	NPD7074	Phase 3
0.7925	Intermediate Similarity	NPD1653	Approved
0.7907	Intermediate Similarity	NPD7090	Clinical (unspecified phase)
0.7895	Intermediate Similarity	NPD4338	Clinical (unspecified phase)
0.787	Intermediate Similarity	NPD7054	Approved
0.7866	Intermediate Similarity	NPD7075	Discontinued
0.7857	Intermediate Similarity	NPD7266	Discontinued
0.7836	Intermediate Similarity	NPD6559	Discontinued
0.7831	Intermediate Similarity	NPD8127	Discontinued
0.7826	Intermediate Similarity	NPD4380	Phase 2
0.7824	Intermediate Similarity	NPD7472	Approved
0.7821	Intermediate Similarity	NPD4628	Phase 3
0.7808	Intermediate Similarity	NPD4379	Clinical (unspecified phase)
0.78	Intermediate Similarity	NPD3764	Approved
0.7785	Intermediate Similarity	NPD1529	Clinical (unspecified phase)
0.7785	Intermediate Similarity	NPD1511	Approved
0.7748	Intermediate Similarity	NPD6233	Phase 2
0.7744	Intermediate Similarity	NPD5402	Approved
0.7727	Intermediate Similarity	NPD8397	Clinical (unspecified phase)
0.7718	Intermediate Similarity	NPD1530	Clinical (unspecified phase)
0.7707	Intermediate Similarity	NPD4109	Clinical (unspecified phase)
0.7707	Intermediate Similarity	NPD8166	Discontinued
0.7707	Intermediate Similarity	NPD4110	Phase 3
0.7707	Intermediate Similarity	NPD3750	Approved
0.7707	Intermediate Similarity	NPD6398	Clinical (unspecified phase)
0.7705	Intermediate Similarity	NPD7680	Approved
0.7697	Intermediate Similarity	NPD7768	Phase 2
0.7688	Intermediate Similarity	NPD1512	Approved
0.7683	Intermediate Similarity	NPD7096	Clinical (unspecified phase)
0.7683	Intermediate Similarity	NPD7819	Suspended
0.7682	Intermediate Similarity	NPD6859	Clinical (unspecified phase)
0.7682	Intermediate Similarity	NPD6798	Discontinued
0.768	Intermediate Similarity	NPD7237	Clinical (unspecified phase)
0.7679	Intermediate Similarity	NPD7229	Phase 3
0.7674	Intermediate Similarity	NPD6797	Phase 2
0.7669	Intermediate Similarity	NPD7411	Suspended
0.7667	Intermediate Similarity	NPD4908	Phase 1
0.7651	Intermediate Similarity	NPD4381	Clinical (unspecified phase)
0.7647	Intermediate Similarity	NPD6355	Discontinued
0.7636	Intermediate Similarity	NPD8443	Clinical (unspecified phase)
0.7633	Intermediate Similarity	NPD5242	Approved
0.763	Intermediate Similarity	NPD7251	Discontinued
0.7625	Intermediate Similarity	NPD2533	Approved
0.7625	Intermediate Similarity	NPD2534	Approved
0.7625	Intermediate Similarity	NPD2532	Approved
0.7625	Intermediate Similarity	NPD7004	Clinical (unspecified phase)
0.7622	Intermediate Similarity	NPD6801	Discontinued
0.7586	Intermediate Similarity	NPD7808	Phase 3
0.758	Intermediate Similarity	NPD970	Clinical (unspecified phase)
0.7566	Intermediate Similarity	NPD4907	Clinical (unspecified phase)
0.7564	Intermediate Similarity	NPD2935	Discontinued
0.7562	Intermediate Similarity	NPD4357	Discontinued
0.7562	Intermediate Similarity	NPD6799	Approved
0.7545	Intermediate Similarity	NPD3749	Approved
0.7532	Intermediate Similarity	NPD7421	Clinical (unspecified phase)
0.7531	Intermediate Similarity	NPD5403	Approved
0.753	Intermediate Similarity	NPD5353	Approved
0.7529	Intermediate Similarity	NPD3926	Phase 2
0.75	Intermediate Similarity	NPD6599	Discontinued
0.75	Intermediate Similarity	NPD1510	Phase 2
0.7486	Intermediate Similarity	NPD7549	Discontinued
0.7485	Intermediate Similarity	NPD7852	Clinical (unspecified phase)
0.7483	Intermediate Similarity	NPD9494	Approved
0.7468	Intermediate Similarity	NPD1549	Phase 2
0.7467	Intermediate Similarity	NPD2797	Approved
0.7455	Intermediate Similarity	NPD7615	Clinical (unspecified phase)
0.744	Intermediate Similarity	NPD6971	Discontinued
0.7419	Intermediate Similarity	NPD447	Suspended
0.7412	Intermediate Similarity	NPD6959	Discontinued
0.7407	Intermediate Similarity	NPD4378	Clinical (unspecified phase)
0.7407	Intermediate Similarity	NPD7410	Clinical (unspecified phase)
0.7407	Intermediate Similarity	NPD5401	Approved
0.7405	Intermediate Similarity	NPD1552	Clinical (unspecified phase)
0.7405	Intermediate Similarity	NPD1550	Clinical (unspecified phase)
0.7396	Intermediate Similarity	NPD919	Approved
0.7389	Intermediate Similarity	NPD3748	Approved
0.7386	Intermediate Similarity	NPD7095	Approved
0.7383	Intermediate Similarity	NPD1608	Approved
0.7383	Intermediate Similarity	NPD9269	Phase 2
0.7365	Intermediate Similarity	NPD8455	Phase 2
0.7362	Intermediate Similarity	NPD6273	Approved
0.7355	Intermediate Similarity	NPD3620	Phase 2
0.7355	Intermediate Similarity	NPD4060	Phase 1
0.7355	Intermediate Similarity	NPD3619	Clinical (unspecified phase)
0.7355	Intermediate Similarity	NPD1240	Approved
0.7355	Intermediate Similarity	NPD943	Approved
0.7349	Intermediate Similarity	NPD6386	Approved
0.7349	Intermediate Similarity	NPD6385	Approved
0.7345	Intermediate Similarity	NPD8312	Approved
0.7345	Intermediate Similarity	NPD8313	Approved
0.7342	Intermediate Similarity	NPD1551	Phase 2
0.7342	Intermediate Similarity	NPD2438	Suspended
0.7342	Intermediate Similarity	NPD2796	Approved
0.7338	Intermediate Similarity	NPD3268	Approved
0.7333	Intermediate Similarity	NPD5808	Clinical (unspecified phase)
0.7333	Intermediate Similarity	NPD2983	Phase 2
0.7333	Intermediate Similarity	NPD2982	Phase 2
0.733	Intermediate Similarity	NPD7039	Approved
0.733	Intermediate Similarity	NPD7038	Approved
0.7329	Intermediate Similarity	NPD5536	Phase 2
0.7318	Intermediate Similarity	NPD8434	Phase 2
0.7315	Intermediate Similarity	NPD1610	Phase 2
0.7299	Intermediate Similarity	NPD3751	Discontinued
0.7292	Intermediate Similarity	NPD5283	Phase 1
0.7267	Intermediate Similarity	NPD1878	Clinical (unspecified phase)
0.7267	Intermediate Similarity	NPD2981	Phase 2
0.7261	Intermediate Similarity	NPD1607	Approved
0.7261	Intermediate Similarity	NPD6653	Approved
0.7257	Intermediate Similarity	NPD7804	Clinical (unspecified phase)
0.7255	Intermediate Similarity	NPD2861	Phase 2
0.7255	Intermediate Similarity	NPD3018	Phase 2
0.7253	Intermediate Similarity	NPD7879	Clinical (unspecified phase)
0.7251	Intermediate Similarity	NPD6746	Phase 2
0.7233	Intermediate Similarity	NPD6100	Approved
0.7233	Intermediate Similarity	NPD6099	Approved
0.7229	Intermediate Similarity	NPD3226	Approved
0.7229	Intermediate Similarity	NPD3455	Phase 2
0.7215	Intermediate Similarity	NPD7097	Phase 1
0.7209	Intermediate Similarity	NPD1247	Approved
0.7205	Intermediate Similarity	NPD1652	Phase 2
0.72	Intermediate Similarity	NPD422	Phase 1
0.72	Intermediate Similarity	NPD3705	Approved
0.7197	Intermediate Similarity	NPD5124	Phase 1
0.7197	Intermediate Similarity	NPD5123	Clinical (unspecified phase)
0.7195	Intermediate Similarity	NPD7422	Clinical (unspecified phase)
0.7188	Intermediate Similarity	NPD6006	Clinical (unspecified phase)
0.7188	Intermediate Similarity	NPD6003	Clinical (unspecified phase)
0.7188	Intermediate Similarity	NPD6005	Phase 3
0.7188	Intermediate Similarity	NPD6004	Phase 3
0.7188	Intermediate Similarity	NPD2343	Clinical (unspecified phase)
0.7188	Intermediate Similarity	NPD6002	Phase 3
0.7186	Intermediate Similarity	NPD7028	Phase 2
0.7181	Intermediate Similarity	NPD17	Approved
0.7179	Intermediate Similarity	NPD4062	Phase 3
0.7171	Intermediate Similarity	NPD1283	Approved
0.717	Intermediate Similarity	NPD2799	Discontinued
0.717	Intermediate Similarity	NPD7033	Discontinued
0.7168	Intermediate Similarity	NPD3787	Discontinued
0.716	Intermediate Similarity	NPD7003	Approved
0.7153	Intermediate Similarity	NPD228	Approved
0.7143	Intermediate Similarity	NPD5958	Discontinued
0.7134	Intermediate Similarity	NPD2979	Phase 3
0.7126	Intermediate Similarity	NPD7458	Discontinued
0.7114	Intermediate Similarity	NPD9268	Approved
0.7108	Intermediate Similarity	NPD920	Approved
0.7089	Intermediate Similarity	NPD1933	Approved
0.7078	Intermediate Similarity	NPD5647	Approved
0.707	Intermediate Similarity	NPD6663	Approved
0.7069	Intermediate Similarity	NPD5711	Approved
0.7069	Intermediate Similarity	NPD5710	Approved
0.7048	Intermediate Similarity	NPD7314	Clinical (unspecified phase)
0.7047	Intermediate Similarity	NPD9545	Approved
0.7047	Intermediate Similarity	NPD8151	Discontinued
0.7047	Intermediate Similarity	NPD1548	Phase 1
0.7037	Intermediate Similarity	NPD4534	Discontinued
0.7033	Intermediate Similarity	NPD8150	Discontinued
0.7032	Intermediate Similarity	NPD5736	Approved
0.7026	Intermediate Similarity	NPD7827	Phase 1
0.7025	Intermediate Similarity	NPD4140	Approved
0.7014	Intermediate Similarity	NPD3021	Approved
0.7014	Intermediate Similarity	NPD3022	Approved
0.7013	Intermediate Similarity	NPD3267	Approved
0.7013	Intermediate Similarity	NPD3266	Approved
0.7012	Intermediate Similarity	NPD5307	Clinical (unspecified phase)
0.7	Intermediate Similarity	NPD5585	Approved
0.6994	Remote Similarity	NPD2800	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