NPASS Compound

Structure

NPC471152 OpenBabel07101718242D 34 37 0 0 1 0 0 0 0 0999 V2000 -1.7321 -3.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7321 0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2321 -0.8660 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 1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.9282 -3.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.0622 -1.5000 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 -7.7942 -3.5000 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 -5.1962 -2.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4641 -2.0000 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 0.0000 1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4641 -3.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.7942 -1.5000 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 -2.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.9282 -2.0000 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 -0.8660 -1.5000 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -8.6603 -3.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.6603 -2.0000 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 0.8660 -0.5000 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -5.1962 -3.0000 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 1.7321 0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 -0.0000 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -9.5263 -3.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -9.5263 -1.5000 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 -6.0622 -3.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.3301 -3.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1 18 2 0 0 0 0 2 28 1 0 0 0 0 3 28 1 0 0 0 0 5 13 1 0 0 0 0 5 14 1 0 0 0 0 6 9 2 0 0 0 0 6 19 1 0 0 0 0 7 11 2 0 0 0 0 7 19 1 0 0 0 0 8 10 1 0 0 0 0 9 22 1 0 0 0 0 10 25 1 0 0 0 0 11 26 1 0 0 0 0 12 15 1 0 0 0 0 12 20 1 0 0 0 0 13 28 1 0 0 0 0 14 29 1 0 0 0 0 15 34 1 0 0 0 0 16 19 2 0 0 0 0 16 23 1 0 0 0 0 17 20 2 0 0 0 0 17 24 1 0 0 0 0 18 20 1 0 0 0 0 18 21 1 0 0 0 0 21 8 1 1 0 0 0 21 27 1 0 0 0 0 22 23 2 0 0 0 0 22 30 1 0 0 0 0 23 31 1 0 0 0 0 24 27 1 0 0 0 0 24 32 2 0 0 0 0 25 28 1 0 0 0 0 25 29 1 6 0 0 0 26 33 2 0 0 0 0 26 34 1 0 0 0 0 27 29 1 6 0 0 0 29 4 1 6 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	464.26
Volume:	498.774
LogP:	5.231
LogD:	4.129
LogS:	-4.505
# Rotatable Bonds:	5
TPSA:	83.83
# H-Bond Aceptor:	5
# H-Bond Donor:	2
# Rings:	4
# Heavy Atoms:	5

MedChem Properties

QED Drug-Likeness Score:	0.326
Synthetic Accessibility Score:	4.469
Fsp3:	0.517
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Accepted
GSK Rule:	Rejected
BMS Rule:	0
Golden Triangle Rule:	Accepted
Chelating Alert:	1
PAINS Alert:	1

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-5.259
MDCK Permeability:	2.2497968529933132e-05
Pgp-inhibitor:	0.999
Pgp-substrate:	0.001
Human Intestinal Absorption (HIA):	0.013
20% Bioavailability (F20%):	0.749
30% Bioavailability (F30%):	0.553

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.058
Plasma Protein Binding (PPB):	97.72771453857422%
Volume Distribution (VD):	0.528
Pgp-substrate:	1.1182186603546143%

ADMET: Metabolism

CYP1A2-inhibitor:	0.355
CYP1A2-substrate:	0.389
CYP2C19-inhibitor:	0.786
CYP2C19-substrate:	0.206
CYP2C9-inhibitor:	0.568
CYP2C9-substrate:	0.917
CYP2D6-inhibitor:	0.772
CYP2D6-substrate:	0.862
CYP3A4-inhibitor:	0.628
CYP3A4-substrate:	0.329

ADMET: Excretion

Clearance (CL):	18.751
Half-life (T1/2):	0.792

ADMET: Toxicity

hERG Blockers:	0.505
Human Hepatotoxicity (H-HT):	0.197
Drug-inuced Liver Injury (DILI):	0.079
AMES Toxicity:	0.067
Rat Oral Acute Toxicity:	0.731
Maximum Recommended Daily Dose:	0.892
Skin Sensitization:	0.954
Carcinogencity:	0.51
Eye Corrosion:	0.013
Eye Irritation:	0.309
Respiratory Toxicity:	0.95

Download Data

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

Natural Product: NPC471152

Natural Product ID:	NPC471152
*Common Name:**	16-O-Caffeoyl-11-Oxocassa-12,14-Diene
IUPAC Name:	2-[(4aS,4bS,8aS,10aR)-4b,8,8-trimethyl-1-methylidene-4-oxo-4a,5,6,7,8a,9,10,10a-octahydrophenanthren-2-yl]ethyl (E)-3-(3,4-dihydroxyphenyl)prop-2-enoate
Synonyms:
Standard InCHIKey:	NUXCVQJWVRCNMX-CYELNHJYSA-N
Standard InCHI:	InChI=1S/C29H36O5/c1-18-20(12-15-34-26(33)11-7-19-6-9-22(30)23(31)16-19)17-24(32)27-21(18)8-10-25-28(2,3)13-5-14-29(25,27)4/h6-7,9,11,16-17,21,25,27,30-31H,1,5,8,10,12-15H2,2-4H3/b11-7+/t21-,25-,27+,29-/m0/s1
SMILES:	CC1(CCCC2(C1CCC3C2C(=O)C=C(C3=C)CCOC(=O)C=CC4=CC(=C(C=C4)O)O)C)C
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL2381685
PubChem CID:	71615304
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001551] 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
NPO33322	caesalpinia volkensii	Species	Fabaceae	Eukaryota	stem bark	n.a.	n.a.	PMID[23562058]

☑ 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
IC50	2

Activity Type	# Activity
Organism	2

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	IC50	=	16530.0	nM	PMID[495864]
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	IC50	=	11630.0	nM	PMID[495864]

☑ 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 NPC471152 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	294
0.1-0.2	1218
0.2-0.3	2364
0.3-0.4	4952
0.4-0.5	9793
0.5-0.6	8936
0.6-0.7	11919
0.7-0.8	2970
0.8-0.85	175
0.85-0.9	69
0.9-0.95	6
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
0.9485	High Similarity	NPC477873
0.9485	High Similarity	NPC469447
0.9348	High Similarity	NPC53520
0.9254	High Similarity	NPC43353
0.9143	High Similarity	NPC8102
0.9143	High Similarity	NPC66894
0.9077	High Similarity	NPC137416
0.9058	High Similarity	NPC27518
0.9058	High Similarity	NPC304110
0.9051	High Similarity	NPC182249
0.8986	High Similarity	NPC473591
0.8986	High Similarity	NPC271494
0.8986	High Similarity	NPC155192
0.8971	High Similarity	NPC173569
0.8971	High Similarity	NPC477874
0.8958	High Similarity	NPC118033
0.8958	High Similarity	NPC473579
0.8958	High Similarity	NPC475454
0.8958	High Similarity	NPC475311
0.8958	High Similarity	NPC473680
0.8905	High Similarity	NPC249817
0.8897	High Similarity	NPC475579
0.8897	High Similarity	NPC473773
0.8865	High Similarity	NPC25491
0.8841	High Similarity	NPC216940
0.8841	High Similarity	NPC475482
0.8841	High Similarity	NPC22676
0.8841	High Similarity	NPC198621
0.8824	High Similarity	NPC476282
0.8806	High Similarity	NPC30174
0.8794	High Similarity	NPC235557
0.8786	High Similarity	NPC470035
0.8786	High Similarity	NPC473612
0.8777	High Similarity	NPC132723
0.8777	High Similarity	NPC76032
0.8732	High Similarity	NPC26045
0.8723	High Similarity	NPC35212
0.8712	High Similarity	NPC265413
0.8712	High Similarity	NPC10154
0.8707	High Similarity	NPC105942
0.8707	High Similarity	NPC205392
0.869	High Similarity	NPC264229
0.869	High Similarity	NPC46549
0.8686	High Similarity	NPC18982
0.8686	High Similarity	NPC475457
0.8686	High Similarity	NPC475627
0.8686	High Similarity	NPC475346
0.8676	High Similarity	NPC243305
0.8671	High Similarity	NPC307205
0.8671	High Similarity	NPC271607
0.8671	High Similarity	NPC280717
0.8662	High Similarity	NPC184935
0.8662	High Similarity	NPC252133
0.8662	High Similarity	NPC310621
0.8652	High Similarity	NPC472801
0.8652	High Similarity	NPC172311
0.8643	High Similarity	NPC234548
0.8643	High Similarity	NPC248287
0.8623	High Similarity	NPC194970
0.8611	High Similarity	NPC75295
0.8611	High Similarity	NPC258856
0.8592	High Similarity	NPC472410
0.8582	High Similarity	NPC471875
0.8571	High Similarity	NPC474532
0.8542	High Similarity	NPC235195
0.8542	High Similarity	NPC19862
0.8529	High Similarity	NPC470747
0.8529	High Similarity	NPC86257
0.8521	High Similarity	NPC29599
0.8511	High Similarity	NPC469680
0.8511	High Similarity	NPC469681
0.8511	High Similarity	NPC471974
0.8511	High Similarity	NPC116742
0.8511	High Similarity	NPC139243
0.85	High Similarity	NPC7464
0.85	High Similarity	NPC476699
0.8489	Intermediate Similarity	NPC471913
0.8462	Intermediate Similarity	NPC203124
0.8451	Intermediate Similarity	NPC470616
0.8451	Intermediate Similarity	NPC470617
0.8433	Intermediate Similarity	NPC15127
0.8433	Intermediate Similarity	NPC288945
0.8425	Intermediate Similarity	NPC472938
0.8425	Intermediate Similarity	NPC472937
0.8425	Intermediate Similarity	NPC273798
0.8425	Intermediate Similarity	NPC472936
0.8414	Intermediate Similarity	NPC8493
0.8414	Intermediate Similarity	NPC144247
0.8414	Intermediate Similarity	NPC469375
0.8414	Intermediate Similarity	NPC294679
0.8414	Intermediate Similarity	NPC145301
0.8411	Intermediate Similarity	NPC471968
0.8409	Intermediate Similarity	NPC470848
0.8409	Intermediate Similarity	NPC470849
0.8403	Intermediate Similarity	NPC469855
0.8403	Intermediate Similarity	NPC471971
0.8403	Intermediate Similarity	NPC471972
0.8403	Intermediate Similarity	NPC30846
0.8397	Intermediate Similarity	NPC42657
0.8397	Intermediate Similarity	NPC263386
0.8397	Intermediate Similarity	NPC141791
0.8394	Intermediate Similarity	NPC131684
0.8392	Intermediate Similarity	NPC78987
0.8392	Intermediate Similarity	NPC82336
0.838	Intermediate Similarity	NPC469857
0.838	Intermediate Similarity	NPC23667
0.838	Intermediate Similarity	NPC477849
0.838	Intermediate Similarity	NPC46242
0.838	Intermediate Similarity	NPC473779
0.838	Intermediate Similarity	NPC473479
0.838	Intermediate Similarity	NPC50615
0.838	Intermediate Similarity	NPC289358
0.838	Intermediate Similarity	NPC245760
0.838	Intermediate Similarity	NPC91887
0.838	Intermediate Similarity	NPC114333
0.838	Intermediate Similarity	NPC157284
0.838	Intermediate Similarity	NPC165191
0.838	Intermediate Similarity	NPC28592
0.838	Intermediate Similarity	NPC5014
0.838	Intermediate Similarity	NPC149773
0.838	Intermediate Similarity	NPC42384
0.838	Intermediate Similarity	NPC51531
0.838	Intermediate Similarity	NPC297797
0.8378	Intermediate Similarity	NPC470619
0.8378	Intermediate Similarity	NPC208785
0.8378	Intermediate Similarity	NPC470618
0.8378	Intermediate Similarity	NPC145527
0.8378	Intermediate Similarity	NPC327962
0.8369	Intermediate Similarity	NPC90431
0.8367	Intermediate Similarity	NPC96930
0.8367	Intermediate Similarity	NPC32017
0.8356	Intermediate Similarity	NPC470038
0.8345	Intermediate Similarity	NPC209085
0.8345	Intermediate Similarity	NPC199936
0.8345	Intermediate Similarity	NPC224884
0.8333	Intermediate Similarity	NPC266084
0.8333	Intermediate Similarity	NPC473544
0.8333	Intermediate Similarity	NPC475145
0.8333	Intermediate Similarity	NPC475162
0.8333	Intermediate Similarity	NPC475216
0.8333	Intermediate Similarity	NPC475595
0.8333	Intermediate Similarity	NPC83663
0.8322	Intermediate Similarity	NPC294330
0.8321	Intermediate Similarity	NPC309434
0.8312	Intermediate Similarity	NPC266365
0.8311	Intermediate Similarity	NPC132810
0.8311	Intermediate Similarity	NPC273358
0.8311	Intermediate Similarity	NPC292206
0.8311	Intermediate Similarity	NPC298647
0.831	Intermediate Similarity	NPC277559
0.8299	Intermediate Similarity	NPC474991
0.8299	Intermediate Similarity	NPC471970
0.8298	Intermediate Similarity	NPC472804
0.8298	Intermediate Similarity	NPC103082
0.8298	Intermediate Similarity	NPC252343
0.8288	Intermediate Similarity	NPC469854
0.8288	Intermediate Similarity	NPC469856
0.8286	Intermediate Similarity	NPC168799
0.8286	Intermediate Similarity	NPC155209
0.8284	Intermediate Similarity	NPC478058
0.8278	Intermediate Similarity	NPC305710
0.8278	Intermediate Similarity	NPC62051
0.8276	Intermediate Similarity	NPC229218
0.8276	Intermediate Similarity	NPC141817
0.8276	Intermediate Similarity	NPC176030
0.8276	Intermediate Similarity	NPC285550
0.8276	Intermediate Similarity	NPC192597
0.8276	Intermediate Similarity	NPC169214
0.8273	Intermediate Similarity	NPC198388
0.8267	Intermediate Similarity	NPC221249
0.8267	Intermediate Similarity	NPC124842
0.8264	Intermediate Similarity	NPC473527
0.8264	Intermediate Similarity	NPC38473
0.8255	Intermediate Similarity	NPC261322
0.8255	Intermediate Similarity	NPC142654
0.8255	Intermediate Similarity	NPC472939
0.8255	Intermediate Similarity	NPC237441
0.8243	Intermediate Similarity	NPC325032
0.8243	Intermediate Similarity	NPC477483
0.8239	Intermediate Similarity	NPC120852
0.8239	Intermediate Similarity	NPC470733
0.8235	Intermediate Similarity	NPC197832
0.8231	Intermediate Similarity	NPC84786
0.8231	Intermediate Similarity	NPC474967
0.8227	Intermediate Similarity	NPC68779
0.8227	Intermediate Similarity	NPC176814
0.8227	Intermediate Similarity	NPC11266
0.8227	Intermediate Similarity	NPC471110
0.8227	Intermediate Similarity	NPC4982
0.8227	Intermediate Similarity	NPC106406
0.8227	Intermediate Similarity	NPC5310
0.8227	Intermediate Similarity	NPC300776
0.8219	Intermediate Similarity	NPC183824
0.8214	Intermediate Similarity	NPC165612
0.8214	Intermediate Similarity	NPC61
0.8214	Intermediate Similarity	NPC5419
0.8214	Intermediate Similarity	NPC18074
0.8214	Intermediate Similarity	NPC25581
0.8214	Intermediate Similarity	NPC239302
0.8209	Intermediate Similarity	NPC147654

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 NPC471152 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	252
0.1-0.2	805
0.2-0.3	1356
0.3-0.4	2424
0.4-0.5	2258
0.5-0.6	1358
0.6-0.7	627
0.7-0.8	69
0.8-0.85	0
0.85-0.9	0
0.9-0.95	1
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.9701	High Similarity	NPD8166	Discontinued
0.8273	Intermediate Similarity	NPD6663	Approved
0.8248	Intermediate Similarity	NPD5736	Approved
0.806	Intermediate Similarity	NPD2932	Approved
0.806	Intermediate Similarity	NPD3019	Approved
0.7848	Intermediate Similarity	NPD8127	Discontinued
0.7815	Intermediate Similarity	NPD6273	Approved
0.7785	Intermediate Similarity	NPD6190	Approved
0.7778	Intermediate Similarity	NPD7458	Discontinued
0.7762	Intermediate Similarity	NPD8032	Phase 2
0.7755	Intermediate Similarity	NPD7266	Discontinued
0.7727	Intermediate Similarity	NPD7028	Phase 2
0.7718	Intermediate Similarity	NPD4109	Clinical (unspecified phase)
0.7718	Intermediate Similarity	NPD7003	Approved
0.7718	Intermediate Similarity	NPD4110	Phase 3
0.7698	Intermediate Similarity	NPD4379	Clinical (unspecified phase)
0.7634	Intermediate Similarity	NPD3022	Approved
0.7634	Intermediate Similarity	NPD3021	Approved
0.7622	Intermediate Similarity	NPD7095	Approved
0.7609	Intermediate Similarity	NPD3026	Approved
0.7609	Intermediate Similarity	NPD3023	Approved
0.76	Intermediate Similarity	NPD6398	Clinical (unspecified phase)
0.76	Intermediate Similarity	NPD4628	Phase 3
0.7591	Intermediate Similarity	NPD3024	Approved
0.7591	Intermediate Similarity	NPD3025	Approved
0.7586	Intermediate Similarity	NPD3620	Phase 2
0.7586	Intermediate Similarity	NPD3619	Clinical (unspecified phase)
0.7569	Intermediate Similarity	NPD3764	Approved
0.756	Intermediate Similarity	NPD8055	Clinical (unspecified phase)
0.7534	Intermediate Similarity	NPD230	Phase 1
0.7518	Intermediate Similarity	NPD1283	Approved
0.7516	Intermediate Similarity	NPD7422	Clinical (unspecified phase)
0.75	Intermediate Similarity	NPD5952	Clinical (unspecified phase)
0.75	Intermediate Similarity	NPD6234	Discontinued
0.7466	Intermediate Similarity	NPD825	Approved
0.7466	Intermediate Similarity	NPD4140	Approved
0.7466	Intermediate Similarity	NPD4060	Phase 1
0.7466	Intermediate Similarity	NPD826	Approved
0.7451	Intermediate Similarity	NPD6143	Clinical (unspecified phase)
0.7436	Intermediate Similarity	NPD3455	Phase 2
0.7429	Intermediate Similarity	NPD3092	Approved
0.7427	Intermediate Similarity	NPD8397	Clinical (unspecified phase)
0.7415	Intermediate Similarity	NPD6355	Discontinued
0.7394	Intermediate Similarity	NPD7228	Approved
0.7391	Intermediate Similarity	NPD3091	Approved
0.7386	Intermediate Similarity	NPD7236	Approved
0.7375	Intermediate Similarity	NPD4868	Clinical (unspecified phase)
0.7353	Intermediate Similarity	NPD2629	Approved
0.7347	Intermediate Similarity	NPD2979	Phase 3
0.7343	Intermediate Similarity	NPD3094	Phase 2
0.7333	Intermediate Similarity	NPD7473	Discontinued
0.7333	Intermediate Similarity	NPD5405	Approved
0.7333	Intermediate Similarity	NPD5406	Approved
0.7333	Intermediate Similarity	NPD5408	Approved
0.7333	Intermediate Similarity	NPD5404	Approved
0.7333	Intermediate Similarity	NPD2935	Discontinued
0.7329	Intermediate Similarity	NPD6798	Discontinued
0.7325	Intermediate Similarity	NPD5808	Clinical (unspecified phase)
0.7305	Intermediate Similarity	NPD1281	Approved
0.7303	Intermediate Similarity	NPD7421	Clinical (unspecified phase)
0.7299	Intermediate Similarity	NPD4198	Discontinued
0.7296	Intermediate Similarity	NPD37	Approved
0.7286	Intermediate Similarity	NPD4626	Approved
0.7267	Intermediate Similarity	NPD3299	Clinical (unspecified phase)
0.7267	Intermediate Similarity	NPD4965	Approved
0.7267	Intermediate Similarity	NPD2799	Discontinued
0.7267	Intermediate Similarity	NPD4967	Phase 2
0.7267	Intermediate Similarity	NPD4966	Approved
0.7266	Intermediate Similarity	NPD9545	Approved
0.726	Intermediate Similarity	NPD7008	Discontinued
0.7255	Intermediate Similarity	NPD3750	Approved
0.725	Intermediate Similarity	NPD2393	Clinical (unspecified phase)
0.7246	Intermediate Similarity	NPD5844	Phase 1
0.7241	Intermediate Similarity	NPD9494	Approved
0.7235	Intermediate Similarity	NPD3534	Clinical (unspecified phase)
0.7226	Intermediate Similarity	NPD5951	Approved
0.7222	Intermediate Similarity	NPD2797	Approved
0.7222	Intermediate Similarity	NPD1470	Approved
0.7219	Intermediate Similarity	NPD2438	Suspended
0.7214	Intermediate Similarity	NPD1651	Approved
0.7214	Intermediate Similarity	NPD5691	Approved
0.7211	Intermediate Similarity	NPD3268	Approved
0.7206	Intermediate Similarity	NPD6858	Approved
0.7206	Intermediate Similarity	NPD7094	Approved
0.7194	Intermediate Similarity	NPD5536	Phase 2
0.7183	Intermediate Similarity	NPD1201	Approved
0.7181	Intermediate Similarity	NPD555	Phase 2
0.7181	Intermediate Similarity	NPD5735	Approved
0.7179	Intermediate Similarity	NPD7004	Clinical (unspecified phase)
0.7172	Intermediate Similarity	NPD258	Approved
0.7172	Intermediate Similarity	NPD257	Approved
0.7171	Intermediate Similarity	NPD2346	Discontinued
0.7164	Intermediate Similarity	NPD6831	Clinical (unspecified phase)
0.7163	Intermediate Similarity	NPD7163	Clinical (unspecified phase)
0.7163	Intermediate Similarity	NPD3095	Discontinued
0.7162	Intermediate Similarity	NPD6233	Phase 2
0.7152	Intermediate Similarity	NPD6232	Discontinued
0.7152	Intermediate Similarity	NPD7239	Suspended
0.7143	Intermediate Similarity	NPD7819	Suspended
0.7133	Intermediate Similarity	NPD3972	Approved
0.7125	Intermediate Similarity	NPD6873	Phase 2
0.7114	Intermediate Similarity	NPD943	Approved
0.711	Intermediate Similarity	NPD8150	Discontinued
0.7105	Intermediate Similarity	NPD6100	Approved
0.7105	Intermediate Similarity	NPD2531	Phase 2
0.7105	Intermediate Similarity	NPD6099	Approved
0.7097	Intermediate Similarity	NPD7910	Clinical (unspecified phase)
0.7092	Intermediate Similarity	NPD5585	Approved
0.7086	Intermediate Similarity	NPD7097	Phase 1
0.7083	Intermediate Similarity	NPD5327	Phase 3
0.7081	Intermediate Similarity	NPD1934	Approved
0.707	Intermediate Similarity	NPD4160	Clinical (unspecified phase)
0.7055	Intermediate Similarity	NPD7768	Phase 2
0.7051	Intermediate Similarity	NPD3300	Phase 2
0.7047	Intermediate Similarity	NPD259	Phase 1
0.7042	Intermediate Similarity	NPD3412	Clinical (unspecified phase)
0.7042	Intermediate Similarity	NPD4059	Approved
0.7029	Intermediate Similarity	NPD1241	Discontinued
0.7029	Intermediate Similarity	NPD5283	Phase 1
0.7019	Intermediate Similarity	NPD6677	Suspended
0.7018	Intermediate Similarity	NPD7685	Pre-registration
0.7014	Intermediate Similarity	NPD1608	Approved
0.7014	Intermediate Similarity	NPD9269	Phase 2
0.7013	Intermediate Similarity	NPD4534	Discontinued
0.7012	Intermediate Similarity	NPD7075	Discontinued
0.7007	Intermediate Similarity	NPD228	Approved
0.7	Intermediate Similarity	NPD3226	Approved
0.6994	Remote Similarity	NPD7090	Clinical (unspecified phase)
0.6992	Remote Similarity	NPD5909	Discontinued
0.6988	Remote Similarity	NPD7199	Phase 2
0.6981	Remote Similarity	NPD6980	Clinical (unspecified phase)
0.6972	Remote Similarity	NPD4196	Clinical (unspecified phase)
0.6964	Remote Similarity	NPD6168	Clinical (unspecified phase)
0.6964	Remote Similarity	NPD6167	Clinical (unspecified phase)
0.6964	Remote Similarity	NPD6166	Phase 2
0.6959	Remote Similarity	NPD7993	Clinical (unspecified phase)
0.6957	Remote Similarity	NPD6599	Discontinued
0.6951	Remote Similarity	NPD3882	Suspended
0.6948	Remote Similarity	NPD5762	Approved
0.6948	Remote Similarity	NPD5763	Approved
0.6947	Remote Similarity	NPD3020	Approved
0.6939	Remote Similarity	NPD4624	Approved
0.6939	Remote Similarity	NPD2798	Approved
0.6936	Remote Similarity	NPD8313	Approved
0.6936	Remote Similarity	NPD8312	Approved
0.6933	Remote Similarity	NPD2801	Approved
0.6933	Remote Similarity	NPD7096	Clinical (unspecified phase)
0.6933	Remote Similarity	NPD7961	Discontinued
0.6933	Remote Similarity	NPD1465	Phase 2
0.6933	Remote Similarity	NPD4062	Phase 3
0.6929	Remote Similarity	NPD7157	Approved
0.6928	Remote Similarity	NPD1509	Clinical (unspecified phase)
0.6928	Remote Similarity	NPD3748	Approved
0.6923	Remote Similarity	NPD1778	Approved
0.6919	Remote Similarity	NPD7240	Approved
0.6918	Remote Similarity	NPD1876	Approved
0.6914	Remote Similarity	NPD7411	Suspended
0.6914	Remote Similarity	NPD8434	Phase 2
0.6913	Remote Similarity	NPD3027	Phase 3
0.6908	Remote Similarity	NPD6653	Approved
0.6908	Remote Similarity	NPD6353	Approved
0.6905	Remote Similarity	NPD7184	Clinical (unspecified phase)
0.6903	Remote Similarity	NPD970	Clinical (unspecified phase)
0.6901	Remote Similarity	NPD7074	Phase 3
0.6901	Remote Similarity	NPD1894	Discontinued
0.6899	Remote Similarity	NPD1511	Approved
0.6892	Remote Similarity	NPD9569	Approved
0.689	Remote Similarity	NPD3817	Phase 2
0.689	Remote Similarity	NPD8443	Clinical (unspecified phase)
0.6889	Remote Similarity	NPD3134	Approved
0.6883	Remote Similarity	NPD4476	Approved
0.6883	Remote Similarity	NPD4477	Approved
0.6879	Remote Similarity	NPD9493	Approved
0.6879	Remote Similarity	NPD405	Clinical (unspecified phase)
0.6875	Remote Similarity	NPD7457	Clinical (unspecified phase)
0.6875	Remote Similarity	NPD3496	Discontinued
0.6875	Remote Similarity	NPD3847	Discontinued
0.6871	Remote Similarity	NPD1164	Approved
0.6871	Remote Similarity	NPD3266	Approved
0.6871	Remote Similarity	NPD3267	Approved
0.6867	Remote Similarity	NPD6859	Clinical (unspecified phase)
0.6867	Remote Similarity	NPD2313	Discontinued
0.6859	Remote Similarity	NPD6674	Discontinued
0.6857	Remote Similarity	NPD690	Clinical (unspecified phase)
0.6855	Remote Similarity	NPD7446	Clinical (unspecified phase)
0.6852	Remote Similarity	NPD4380	Phase 2
0.6849	Remote Similarity	NPD4359	Approved
0.6849	Remote Similarity	NPD3600	Clinical (unspecified phase)
0.6846	Remote Similarity	NPD2614	Approved
0.6842	Remote Similarity	NPD274	Approved
0.6842	Remote Similarity	NPD447	Suspended
0.6842	Remote Similarity	NPD275	Approved
0.6842	Remote Similarity	NPD3657	Discovery
0.6842	Remote Similarity	NPD7054	Approved
0.6839	Remote Similarity	NPD2343	Clinical (unspecified phase)
0.6839	Remote Similarity	NPD7702	Clinical (unspecified phase)
0.6838	Remote Similarity	NPD1358	Approved
0.6835	Remote Similarity	NPD7440	Discontinued
0.6835	Remote Similarity	NPD5535	Approved
0.6828	Remote Similarity	NPD1535	Discovery

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