NPASS Compound

Structure

NPC249788 OpenBabel07101719132D 22 24 0 0 1 0 0 0 0 0999 V2000 4.4152 -2.6910 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6831 -1.6910 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4152 0.3090 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.1472 0.3090 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6831 1.3090 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4152 1.3090 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.1472 1.3090 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8171 1.8090 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2812 -1.1910 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5491 -0.1910 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8171 -0.1910 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 4.4152 -1.6910 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 3.5491 -1.1910 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 5.2812 -0.1910 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6831 0.3090 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2812 1.8090 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 0.9511 0.3090 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2812 2.8090 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 1.6180 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 3 6 1 0 0 0 0 3 15 2 0 0 0 0 4 7 2 0 0 0 0 4 15 1 0 0 0 0 5 8 2 0 0 0 0 5 16 1 0 0 0 0 6 17 2 0 0 0 0 7 17 1 0 0 0 0 8 18 1 0 0 0 0 9 13 1 0 0 0 0 9 15 1 0 0 0 0 10 14 1 0 0 0 0 10 16 1 0 0 0 0 11 16 2 0 0 0 0 11 19 1 0 0 0 0 12 21 1 0 0 0 0 12 22 1 0 0 0 0 13 1 1 1 0 0 0 13 14 1 0 0 0 0 14 2 1 6 0 0 0 17 20 1 0 0 0 0 18 19 2 0 0 0 0 18 21 1 0 0 0 0 19 22 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	298.16
Volume:	322.063
LogP:	5.067
LogD:	4.774
LogS:	-5.158
# Rotatable Bonds:	5
TPSA:	38.69
# H-Bond Aceptor:	3
# H-Bond Donor:	1
# Rings:	3
# Heavy Atoms:	3

MedChem Properties

QED Drug-Likeness Score:	0.9
Synthetic Accessibility Score:	2.836
Fsp3:	0.368
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:	-4.853
MDCK Permeability:	2.271672201459296e-05
Pgp-inhibitor:	0.061
Pgp-substrate:	0.002
Human Intestinal Absorption (HIA):	0.002
20% Bioavailability (F20%):	0.012
30% Bioavailability (F30%):	0.119

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.149
Plasma Protein Binding (PPB):	99.24857330322266%
Volume Distribution (VD):	1.136
Pgp-substrate:	1.6193830966949463%

ADMET: Metabolism

CYP1A2-inhibitor:	0.967
CYP1A2-substrate:	0.236
CYP2C19-inhibitor:	0.981
CYP2C19-substrate:	0.32
CYP2C9-inhibitor:	0.893
CYP2C9-substrate:	0.906
CYP2D6-inhibitor:	0.989
CYP2D6-substrate:	0.918
CYP3A4-inhibitor:	0.961
CYP3A4-substrate:	0.717

ADMET: Excretion

Clearance (CL):	18.297
Half-life (T1/2):	0.352

ADMET: Toxicity

hERG Blockers:	0.142
Human Hepatotoxicity (H-HT):	0.106
Drug-inuced Liver Injury (DILI):	0.768
AMES Toxicity:	0.062
Rat Oral Acute Toxicity:	0.04
Maximum Recommended Daily Dose:	0.213
Skin Sensitization:	0.781
Carcinogencity:	0.82
Eye Corrosion:	0.038
Eye Irritation:	0.915
Respiratory Toxicity:	0.138

Download Data

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

Natural Product: NPC249788

Natural Product ID:	NPC249788
*Common Name:**	4'-Hydroxy-3,4-Methylenedioxy-8,8'-Lignan
IUPAC Name:	4-[(2R,3R)-4-(1,3-benzodioxol-5-yl)-2,3-dimethylbutyl]phenol
Synonyms:
Standard InCHIKey:	USIMVYHZXYVIRF-ZIAGYGMSSA-N
Standard InCHI:	InChI=1S/C19H22O3/c1-13(9-15-3-6-17(20)7-4-15)14(2)10-16-5-8-18-19(11-16)22-12-21-18/h3-8,11,13-14,20H,9-10,12H2,1-2H3/t13-,14-/m1/s1
SMILES:	Oc1ccc(cc1)C[C@H]([C@@H](Cc1ccc2c(c1)OCO2)C)C
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL261196
PubChem CID:	44450608
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0001392] Lignans, neolignans and related compounds [CHEMONTID:0001969] Dibenzylbutane lignans

*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
NPO2754	Iryanthera lancifolia	Species	Myristicaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[10579855]
NPO2754	Iryanthera lancifolia	Species	Myristicaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[18242997]
NPO2754	Iryanthera lancifolia	Species	Myristicaceae	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	4

Activity Type	# Activity
Cell Line	4

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT83	Cell Line	MCF7	Homo sapiens	MED	=	10.0	uM	PMID[516377]
NPT83	Cell Line	MCF7	Homo sapiens	Ratio	=	5.8	n.a.	PMID[516377]
NPT83	Cell Line	MCF7	Homo sapiens	Activity	=	0.01	%	PMID[516377]
NPT83	Cell Line	MCF7	Homo sapiens	Activity	=	68.7	%	PMID[516377]

☑ 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 NPC249788 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	328
0.1-0.2	1712
0.2-0.3	4474
0.3-0.4	13394
0.4-0.5	4783
0.5-0.6	6093
0.6-0.7	8347
0.7-0.8	2870
0.8-0.85	557
0.85-0.9	105
0.9-0.95	30
0.95-1	4

Similarity Score	Similarity Level	Natural Product ID
0.9748	High Similarity	NPC274356
0.9487	High Similarity	NPC344161
0.9431	High Similarity	NPC275950
0.9355	High Similarity	NPC476345
0.9328	High Similarity	NPC80241
0.9328	High Similarity	NPC301641
0.928	High Similarity	NPC471505
0.928	High Similarity	NPC106739
0.928	High Similarity	NPC227002
0.9274	High Similarity	NPC181079
0.9274	High Similarity	NPC173308
0.9262	High Similarity	NPC213711
0.9262	High Similarity	NPC40352
0.9237	High Similarity	NPC310338
0.9237	High Similarity	NPC281298
0.9206	High Similarity	NPC169973
0.9174	High Similarity	NPC31344
0.9174	High Similarity	NPC317769
0.916	High Similarity	NPC117780
0.916	High Similarity	NPC95614
0.916	High Similarity	NPC242885
0.916	High Similarity	NPC56214
0.916	High Similarity	NPC227217
0.916	High Similarity	NPC165133
0.916	High Similarity	NPC232316
0.9127	High Similarity	NPC104077
0.9127	High Similarity	NPC219671
0.9127	High Similarity	NPC259742
0.9127	High Similarity	NPC147616
0.912	High Similarity	NPC63574
0.9062	High Similarity	NPC142547
0.9062	High Similarity	NPC135777
0.9062	High Similarity	NPC184938
0.9062	High Similarity	NPC101624
0.9024	High Similarity	NPC17348
0.9008	High Similarity	NPC38996
0.9008	High Similarity	NPC160380
0.8992	High Similarity	NPC474040
0.8992	High Similarity	NPC470626
0.8976	High Similarity	NPC97316
0.8968	High Similarity	NPC134764
0.8968	High Similarity	NPC171550
0.8968	High Similarity	NPC184814
0.8934	High Similarity	NPC30462
0.8934	High Similarity	NPC85488
0.8908	High Similarity	NPC293619
0.8906	High Similarity	NPC196937
0.8889	High Similarity	NPC165106
0.888	High Similarity	NPC177167
0.888	High Similarity	NPC158737
0.8862	High Similarity	NPC280704
0.8855	High Similarity	NPC123526
0.8855	High Similarity	NPC193666
0.8855	High Similarity	NPC88640
0.8846	High Similarity	NPC197166
0.881	High Similarity	NPC226862
0.881	High Similarity	NPC21867
0.881	High Similarity	NPC184733
0.881	High Similarity	NPC45774
0.881	High Similarity	NPC158471
0.881	High Similarity	NPC129570
0.881	High Similarity	NPC282703
0.881	High Similarity	NPC165128
0.881	High Similarity	NPC57119
0.881	High Similarity	NPC128208
0.881	High Similarity	NPC11258
0.8793	High Similarity	NPC31279
0.8788	High Similarity	NPC284464
0.8779	High Similarity	NPC474039
0.877	High Similarity	NPC207613
0.8769	High Similarity	NPC18576
0.876	High Similarity	NPC112237
0.876	High Similarity	NPC471391
0.876	High Similarity	NPC471390
0.874	High Similarity	NPC476748
0.874	High Similarity	NPC475875
0.874	High Similarity	NPC470633
0.874	High Similarity	NPC228769
0.8739	High Similarity	NPC475815
0.8739	High Similarity	NPC47194
0.8739	High Similarity	NPC473264
0.873	High Similarity	NPC100129
0.8722	High Similarity	NPC166137
0.8722	High Similarity	NPC28398
0.8722	High Similarity	NPC472711
0.8722	High Similarity	NPC282291
0.872	High Similarity	NPC228771
0.872	High Similarity	NPC29008
0.872	High Similarity	NPC266705
0.872	High Similarity	NPC9067
0.872	High Similarity	NPC148627
0.8712	High Similarity	NPC9068
0.8712	High Similarity	NPC30951
0.8712	High Similarity	NPC6369
0.8707	High Similarity	NPC127326
0.8699	High Similarity	NPC184651
0.8699	High Similarity	NPC343720
0.8699	High Similarity	NPC113865
0.8699	High Similarity	NPC262156
0.8699	High Similarity	NPC470212
0.8699	High Similarity	NPC312675
0.8699	High Similarity	NPC473853
0.8699	High Similarity	NPC54872
0.8699	High Similarity	NPC324571
0.8692	High Similarity	NPC47181
0.8678	High Similarity	NPC474214
0.8672	High Similarity	NPC233224
0.8672	High Similarity	NPC187998
0.8672	High Similarity	NPC242807
0.8672	High Similarity	NPC145305
0.8672	High Similarity	NPC42300
0.8672	High Similarity	NPC271208
0.8672	High Similarity	NPC153739
0.8672	High Similarity	NPC92164
0.8672	High Similarity	NPC77040
0.8672	High Similarity	NPC257582
0.8672	High Similarity	NPC64201
0.8672	High Similarity	NPC241522
0.8672	High Similarity	NPC174495
0.8667	High Similarity	NPC9341
0.8667	High Similarity	NPC81067
0.8661	High Similarity	NPC470084
0.8661	High Similarity	NPC147247
0.8661	High Similarity	NPC246974
0.8657	High Similarity	NPC52664
0.8651	High Similarity	NPC206882
0.8647	High Similarity	NPC177868
0.8636	High Similarity	NPC185908
0.8626	High Similarity	NPC150534
0.8626	High Similarity	NPC174191
0.8621	High Similarity	NPC201959
0.8621	High Similarity	NPC75440
0.8607	High Similarity	NPC474320
0.8605	High Similarity	NPC27843
0.8605	High Similarity	NPC228346
0.8605	High Similarity	NPC40432
0.8605	High Similarity	NPC161557
0.8605	High Similarity	NPC277804
0.8605	High Similarity	NPC227160
0.8605	High Similarity	NPC7171
0.8605	High Similarity	NPC82111
0.8605	High Similarity	NPC115207
0.8605	High Similarity	NPC158079
0.8605	High Similarity	NPC192255
0.8595	High Similarity	NPC86947
0.8595	High Similarity	NPC164386
0.8593	High Similarity	NPC265154
0.8593	High Similarity	NPC255566
0.8593	High Similarity	NPC298317
0.8593	High Similarity	NPC185307
0.8593	High Similarity	NPC474808
0.8593	High Similarity	NPC470950
0.8593	High Similarity	NPC477898
0.8583	High Similarity	NPC5428
0.8583	High Similarity	NPC165045
0.8583	High Similarity	NPC127587
0.8583	High Similarity	NPC157740
0.8583	High Similarity	NPC64948
0.8583	High Similarity	NPC118533
0.8583	High Similarity	NPC99798
0.8583	High Similarity	NPC191302
0.856	High Similarity	NPC282496
0.856	High Similarity	NPC471693
0.856	High Similarity	NPC233526
0.8559	High Similarity	NPC173746
0.8559	High Similarity	NPC257124
0.8559	High Similarity	NPC8547
0.8559	High Similarity	NPC156840
0.855	High Similarity	NPC300776
0.855	High Similarity	NPC4982
0.855	High Similarity	NPC5310
0.855	High Similarity	NPC68779
0.855	High Similarity	NPC176814
0.855	High Similarity	NPC67247
0.8548	High Similarity	NPC57268
0.8548	High Similarity	NPC216929
0.8548	High Similarity	NPC290451
0.8548	High Similarity	NPC127389
0.8548	High Similarity	NPC65933
0.8548	High Similarity	NPC312713
0.8548	High Similarity	NPC172676
0.8548	High Similarity	NPC126935
0.8538	High Similarity	NPC181049
0.8538	High Similarity	NPC7744
0.8538	High Similarity	NPC207400
0.8529	High Similarity	NPC129417
0.8529	High Similarity	NPC46880
0.8529	High Similarity	NPC283995
0.8529	High Similarity	NPC84181
0.8529	High Similarity	NPC470235
0.8519	High Similarity	NPC133934
0.8519	High Similarity	NPC302506
0.8519	High Similarity	NPC184684
0.8519	High Similarity	NPC191231
0.8519	High Similarity	NPC184641
0.8519	High Similarity	NPC253878
0.8519	High Similarity	NPC476356
0.8516	High Similarity	NPC307050
0.8516	High Similarity	NPC277458
0.8504	High Similarity	NPC76451

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 NPC249788 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	305
0.1-0.2	986
0.2-0.3	1473
0.3-0.4	2779
0.4-0.5	1807
0.5-0.6	1042
0.6-0.7	619
0.7-0.8	131
0.8-0.85	5
0.85-0.9	3
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.8889	High Similarity	NPD5283	Phase 1
0.876	High Similarity	NPD1357	Approved
0.8559	High Similarity	NPD228	Approved
0.84	Intermediate Similarity	NPD3705	Approved
0.8235	Intermediate Similarity	NPD3021	Approved
0.8235	Intermediate Similarity	NPD3022	Approved
0.8168	Intermediate Similarity	NPD3027	Phase 3
0.8125	Intermediate Similarity	NPD4379	Clinical (unspecified phase)
0.812	Intermediate Similarity	NPD3620	Phase 2
0.812	Intermediate Similarity	NPD3619	Clinical (unspecified phase)
0.8071	Intermediate Similarity	NPD6143	Clinical (unspecified phase)
0.7984	Intermediate Similarity	NPD3600	Clinical (unspecified phase)
0.7931	Intermediate Similarity	NPD3020	Approved
0.7857	Intermediate Similarity	NPD5536	Phase 2
0.7852	Intermediate Similarity	NPD4060	Phase 1
0.7801	Intermediate Similarity	NPD5084	Clinical (unspecified phase)
0.7755	Intermediate Similarity	NPD37	Approved
0.7744	Intermediate Similarity	NPD2861	Phase 2
0.774	Intermediate Similarity	NPD7028	Phase 2
0.7705	Intermediate Similarity	NPD2684	Approved
0.7704	Intermediate Similarity	NPD5110	Phase 2
0.7704	Intermediate Similarity	NPD5109	Approved
0.7704	Intermediate Similarity	NPD5111	Phase 2
0.7672	Intermediate Similarity	NPD2860	Approved
0.7672	Intermediate Similarity	NPD2859	Approved
0.7616	Intermediate Similarity	NPD6234	Discontinued
0.7606	Intermediate Similarity	NPD6331	Phase 2
0.7606	Intermediate Similarity	NPD4109	Clinical (unspecified phase)
0.7606	Intermediate Similarity	NPD4110	Phase 3
0.76	Intermediate Similarity	NPD4967	Phase 2
0.76	Intermediate Similarity	NPD4966	Approved
0.76	Intermediate Similarity	NPD4965	Approved
0.7586	Intermediate Similarity	NPD2934	Approved
0.7586	Intermediate Similarity	NPD2933	Approved
0.7584	Intermediate Similarity	NPD2977	Approved
0.7584	Intermediate Similarity	NPD5563	Clinical (unspecified phase)
0.7584	Intermediate Similarity	NPD2978	Approved
0.7576	Intermediate Similarity	NPD2982	Phase 2
0.7576	Intermediate Similarity	NPD2983	Phase 2
0.7559	Intermediate Similarity	NPD6671	Approved
0.7559	Intermediate Similarity	NPD709	Approved
0.7559	Intermediate Similarity	NPD7157	Approved
0.7556	Intermediate Similarity	NPD1529	Clinical (unspecified phase)
0.7538	Intermediate Similarity	NPD4626	Approved
0.7538	Intermediate Similarity	NPD2667	Approved
0.7538	Intermediate Similarity	NPD2668	Approved
0.7537	Intermediate Similarity	NPD4624	Approved
0.7537	Intermediate Similarity	NPD6584	Phase 3
0.7535	Intermediate Similarity	NPD6674	Discontinued
0.7519	Intermediate Similarity	NPD1283	Approved
0.7518	Intermediate Similarity	NPD2674	Phase 3
0.7518	Intermediate Similarity	NPD554	Clinical (unspecified phase)
0.75	Intermediate Similarity	NPD5451	Approved
0.75	Intermediate Similarity	NPD6783	Clinical (unspecified phase)
0.75	Intermediate Similarity	NPD2232	Approved
0.75	Intermediate Similarity	NPD2230	Approved
0.75	Intermediate Similarity	NPD2233	Approved
0.75	Intermediate Similarity	NPD4108	Discontinued
0.75	Intermediate Similarity	NPD2981	Phase 2
0.75	Intermediate Similarity	NPD7095	Approved
0.7481	Intermediate Similarity	NPD1530	Clinical (unspecified phase)
0.7481	Intermediate Similarity	NPD3018	Phase 2
0.7464	Intermediate Similarity	NPD1558	Phase 1
0.7464	Intermediate Similarity	NPD1612	Clinical (unspecified phase)
0.7464	Intermediate Similarity	NPD1613	Approved
0.746	Intermediate Similarity	NPD7843	Approved
0.7447	Intermediate Similarity	NPD2161	Phase 2
0.7445	Intermediate Similarity	NPD3144	Approved
0.7445	Intermediate Similarity	NPD3145	Approved
0.7429	Intermediate Similarity	NPD6895	Approved
0.7429	Intermediate Similarity	NPD6896	Approved
0.7426	Intermediate Similarity	NPD5752	Clinical (unspecified phase)
0.7426	Intermediate Similarity	NPD4908	Phase 1
0.7424	Intermediate Similarity	NPD1610	Phase 2
0.7415	Intermediate Similarity	NPD6980	Clinical (unspecified phase)
0.7413	Intermediate Similarity	NPD3060	Approved
0.741	Intermediate Similarity	NPD3657	Discovery
0.741	Intermediate Similarity	NPD6355	Discontinued
0.7403	Intermediate Similarity	NPD7199	Phase 2
0.7398	Intermediate Similarity	NPD968	Approved
0.7394	Intermediate Similarity	NPD7266	Discontinued
0.7394	Intermediate Similarity	NPD1375	Discontinued
0.7376	Intermediate Similarity	NPD6028	Clinical (unspecified phase)
0.7376	Intermediate Similarity	NPD6029	Clinical (unspecified phase)
0.7357	Intermediate Similarity	NPD2492	Phase 1
0.7348	Intermediate Similarity	NPD3847	Discontinued
0.7338	Intermediate Similarity	NPD4140	Approved
0.7328	Intermediate Similarity	NPD1651	Approved
0.7323	Intermediate Similarity	NPD1138	Approved
0.7323	Intermediate Similarity	NPD5535	Approved
0.7319	Intermediate Similarity	NPD4907	Clinical (unspecified phase)
0.7319	Intermediate Similarity	NPD5718	Phase 2
0.7313	Intermediate Similarity	NPD5327	Phase 3
0.7313	Intermediate Similarity	NPD6583	Phase 3
0.7313	Intermediate Similarity	NPD1669	Approved
0.7313	Intermediate Similarity	NPD6582	Phase 2
0.731	Intermediate Similarity	NPD5241	Discontinued
0.7308	Intermediate Similarity	NPD7184	Clinical (unspecified phase)
0.7293	Intermediate Similarity	NPD1281	Approved
0.7292	Intermediate Similarity	NPD4236	Phase 3
0.7292	Intermediate Similarity	NPD5177	Phase 3
0.7292	Intermediate Similarity	NPD4237	Approved
0.7288	Intermediate Similarity	NPD9296	Approved
0.7288	Intermediate Similarity	NPD1432	Clinical (unspecified phase)
0.7287	Intermediate Similarity	NPD6387	Discontinued
0.7286	Intermediate Similarity	NPD5735	Approved
0.7278	Intermediate Similarity	NPD7228	Approved
0.7273	Intermediate Similarity	NPD6516	Phase 2
0.7273	Intermediate Similarity	NPD5846	Approved
0.7266	Intermediate Similarity	NPD1726	Clinical (unspecified phase)
0.7259	Intermediate Similarity	NPD2922	Phase 1
0.7252	Intermediate Similarity	NPD3091	Approved
0.7244	Intermediate Similarity	NPD1137	Approved
0.7244	Intermediate Similarity	NPD1139	Approved
0.7239	Intermediate Similarity	NPD1608	Approved
0.7234	Intermediate Similarity	NPD4097	Suspended
0.7226	Intermediate Similarity	NPD9494	Approved
0.7222	Intermediate Similarity	NPD7037	Approved
0.7208	Intermediate Similarity	NPD5604	Discontinued
0.7197	Intermediate Similarity	NPD5585	Approved
0.7197	Intermediate Similarity	NPD5691	Approved
0.7185	Intermediate Similarity	NPD3685	Discontinued
0.7185	Intermediate Similarity	NPD4749	Approved
0.7171	Intermediate Similarity	NPD7945	Clinical (unspecified phase)
0.7167	Intermediate Similarity	NPD288	Approved
0.7164	Intermediate Similarity	NPD1091	Approved
0.7164	Intermediate Similarity	NPD3092	Approved
0.7153	Intermediate Similarity	NPD2798	Approved
0.7143	Intermediate Similarity	NPD5058	Phase 3
0.7122	Intermediate Similarity	NPD2669	Clinical (unspecified phase)
0.7122	Intermediate Similarity	NPD4625	Phase 3
0.7121	Intermediate Similarity	NPD1548	Phase 1
0.7121	Intermediate Similarity	NPD1182	Approved
0.712	Intermediate Similarity	NPD3134	Approved
0.7114	Intermediate Similarity	NPD5261	Clinical (unspecified phase)
0.7113	Intermediate Similarity	NPD4579	Clinical (unspecified phase)
0.7113	Intermediate Similarity	NPD6353	Approved
0.7111	Intermediate Similarity	NPD1840	Phase 2
0.7111	Intermediate Similarity	NPD2235	Phase 2
0.7111	Intermediate Similarity	NPD2231	Phase 2
0.7103	Intermediate Similarity	NPD2808	Discontinued
0.7103	Intermediate Similarity	NPD4664	Clinical (unspecified phase)
0.7097	Intermediate Similarity	NPD7833	Phase 2
0.7097	Intermediate Similarity	NPD7832	Clinical (unspecified phase)
0.7097	Intermediate Similarity	NPD7831	Phase 2
0.7092	Intermediate Similarity	NPD5837	Clinical (unspecified phase)
0.7092	Intermediate Similarity	NPD2238	Phase 2
0.7086	Intermediate Similarity	NPD7458	Discontinued
0.7083	Intermediate Similarity	NPD2935	Discontinued
0.7083	Intermediate Similarity	NPD844	Approved
0.708	Intermediate Similarity	NPD2797	Approved
0.7078	Intermediate Similarity	NPD2358	Clinical (unspecified phase)
0.7071	Intermediate Similarity	NPD6798	Discontinued
0.7063	Intermediate Similarity	NPD7097	Phase 1
0.7063	Intermediate Similarity	NPD3818	Discontinued
0.7063	Intermediate Similarity	NPD290	Approved
0.7063	Intermediate Similarity	NPD1358	Approved
0.7055	Intermediate Similarity	NPD4162	Approved
0.7054	Intermediate Similarity	NPD821	Approved
0.7054	Intermediate Similarity	NPD7635	Approved
0.7047	Intermediate Similarity	NPD4739	Approved
0.7034	Intermediate Similarity	NPD5763	Approved
0.7034	Intermediate Similarity	NPD5762	Approved
0.7029	Intermediate Similarity	NPD6917	Clinical (unspecified phase)
0.7027	Intermediate Similarity	NPD7124	Phase 2
0.702	Intermediate Similarity	NPD1653	Approved
0.7015	Intermediate Similarity	NPD4059	Approved
0.7015	Intermediate Similarity	NPD3019	Approved
0.7015	Intermediate Similarity	NPD2932	Approved
0.7015	Intermediate Similarity	NPD17	Approved
0.7007	Intermediate Similarity	NPD6696	Suspended
0.7007	Intermediate Similarity	NPD6658	Clinical (unspecified phase)
0.7007	Intermediate Similarity	NPD1876	Approved
0.7	Intermediate Similarity	NPD2229	Approved
0.7	Intermediate Similarity	NPD2234	Approved
0.7	Intermediate Similarity	NPD2228	Approved
0.6993	Remote Similarity	NPD2157	Approved
0.6993	Remote Similarity	NPD6653	Approved
0.6992	Remote Similarity	NPD1242	Phase 1
0.6992	Remote Similarity	NPD1894	Discontinued
0.6992	Remote Similarity	NPD289	Clinical (unspecified phase)
0.6987	Remote Similarity	NPD7975	Clinical (unspecified phase)
0.6986	Remote Similarity	NPD5958	Discontinued
0.698	Remote Similarity	NPD4357	Discontinued
0.6978	Remote Similarity	NPD1712	Approved
0.6978	Remote Similarity	NPD5736	Approved
0.6972	Remote Similarity	NPD2979	Phase 3
0.697	Remote Similarity	NPD7090	Clinical (unspecified phase)
0.697	Remote Similarity	NPD3596	Phase 2
0.6966	Remote Similarity	NPD2438	Suspended
0.6963	Remote Similarity	NPD3496	Discontinued
0.6959	Remote Similarity	NPD5307	Clinical (unspecified phase)
0.6957	Remote Similarity	NPD3094	Phase 2
0.6957	Remote Similarity	NPD987	Approved
0.6953	Remote Similarity	NPD4750	Phase 3
0.6953	Remote Similarity	NPD1792	Phase 2
0.695	Remote Similarity	NPD6410	Clinical (unspecified phase)
0.6944	Remote Similarity	NPD6111	Discontinued
0.694	Remote Similarity	NPD4093	Discontinued
0.6934	Remote Similarity	NPD4359	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