NPASS Compound

Structure

NPC476439 OpenBabel07101719252D 24 25 0 0 1 0 0 0 0 0999 V2000 -0.7787 -1.9380 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3676 -1.2486 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6502 -2.2863 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9944 -0.0179 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6300 2.8728 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3243 -1.3888 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8223 1.3935 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4582 -0.8888 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4843 0.6440 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7132 1.7815 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5094 0.1672 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6582 2.1086 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3201 1.1491 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3741 -1.1346 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3231 -1.3413 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8521 -1.0077 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0951 0.9955 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.9761 -0.2172 0.0000 C 0 0 2 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 3.1377 -0.7612 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 2.6300 1.8728 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 5.6382 -1.6259 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 3.4961 2.3728 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 3.9237 -1.3794 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1 14 1 0 0 0 0 2 14 1 0 0 0 0 3 15 2 0 0 0 0 4 16 1 0 0 0 0 6 8 1 0 0 0 0 6 15 1 0 0 0 0 7 9 1 0 0 0 0 9 18 1 0 0 0 0 10 12 2 0 0 0 0 10 17 1 0 0 0 0 11 13 1 0 0 0 0 11 20 1 0 0 0 0 12 21 1 0 0 0 0 13 21 1 0 0 0 0 15 20 1 0 0 0 0 16 22 2 0 0 0 0 16 24 1 0 0 0 0 17 7 1 6 0 0 0 17 19 1 0 0 0 0 18 14 1 1 0 0 0 18 19 1 0 0 0 0 19 8 1 1 0 0 0 20 24 1 1 0 0 0 21 5 1 1 0 0 0 21 23 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	334.25
Volume:	373.121
LogP:	4.364
LogD:	4.165
LogS:	-5.071
# Rotatable Bonds:	3
TPSA:	46.53
# H-Bond Aceptor:	3
# H-Bond Donor:	1
# Rings:	2
# Heavy Atoms:	3

MedChem Properties

QED Drug-Likeness Score:	0.59
Synthetic Accessibility Score:	4.851
Fsp3:	0.762
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:	-4.468
MDCK Permeability:	2.0325916921137832e-05
Pgp-inhibitor:	0.0
Pgp-substrate:	0.003
Human Intestinal Absorption (HIA):	0.075
20% Bioavailability (F20%):	0.256
30% Bioavailability (F30%):	0.017

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.201
Plasma Protein Binding (PPB):	90.05876922607422%
Volume Distribution (VD):	1.157
Pgp-substrate:	2.0365915298461914%

ADMET: Metabolism

CYP1A2-inhibitor:	0.14
CYP1A2-substrate:	0.412
CYP2C19-inhibitor:	0.296
CYP2C19-substrate:	0.819
CYP2C9-inhibitor:	0.503
CYP2C9-substrate:	0.673
CYP2D6-inhibitor:	0.055
CYP2D6-substrate:	0.41
CYP3A4-inhibitor:	0.909
CYP3A4-substrate:	0.527

ADMET: Excretion

Clearance (CL):	2.982
Half-life (T1/2):	0.267

ADMET: Toxicity

hERG Blockers:	0.046
Human Hepatotoxicity (H-HT):	0.699
Drug-inuced Liver Injury (DILI):	0.872
AMES Toxicity:	0.383
Rat Oral Acute Toxicity:	0.247
Maximum Recommended Daily Dose:	0.77
Skin Sensitization:	0.287
Carcinogencity:	0.536
Eye Corrosion:	0.021
Eye Irritation:	0.219
Respiratory Toxicity:	0.842

Download Data

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

Natural Product: NPC476439

Natural Product ID:	NPC476439
*Common Name:**	Sphaerollane I
IUPAC Name:	[(1R,3aR,4E,6R,9R,12aS)-6-hydroxy-6-methyl-10-methylidene-1-propan-2-yl-1,2,3,3a,7,8,9,11,12,12a-decahydrocyclopenta[11]annulen-9-yl] acetate
Synonyms:	sphaerollane I
Standard InCHIKey:	XBAFJMNDOVYNFK-QHFNRRHCSA-N
Standard InCHI:	InChI=1S/C21H34O3/c1-14(2)18-9-7-17-10-12-21(5,23)13-11-20(24-16(4)22)15(3)6-8-19(17)18/h10,12,14,17-20,23H,3,6-9,11,13H2,1-2,4-5H3/b12-10+/t17-,18-,19-,20-,21+/m1/s1
SMILES:	CC(=O)O[C@@H]1CC[C@@](C)(O)/C=C/[C@@H]2[C@@H](CCC1=C)[C@H](CC2)C(C)C
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL606379
PubChem CID:	46231445
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
NPO29354	Sphaerococcus coronopifolius	Species	Sphaerococcaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[11520219]
NPO29354	Sphaerococcus coronopifolius	Species	Sphaerococcaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[18597527]
NPO29354	Sphaerococcus coronopifolius	Species	Sphaerococcaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[20045651]
NPO29354	Sphaerococcus coronopifolius	Species	Sphaerococcaceae	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
IC50	6

Activity Type	# Activity
Cell Line	4
NON-MOLECULAR	2

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT81	Cell Line	A549	Homo sapiens	IC50	=	44000.0	nM	PMID[469921]
NPT170	Cell Line	SK-MEL-28	Homo sapiens	IC50	=	57000.0	nM	PMID[469921]
NPT306	Cell Line	PC-3	Homo sapiens	IC50	=	34000.0	nM	PMID[469921]
NPT114	Cell Line	LoVo	Homo sapiens	IC50	=	23000.0	nM	PMID[469921]
NPT20529	NON-MOLECULAR	NON-PROTEIN TARGET	n.a.	IC50	=	20000.0	nM	PMID[469921]
NPT20529	NON-MOLECULAR	NON-PROTEIN TARGET	n.a.	IC50	=	34000.0	nM	PMID[469921]

☑ 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 NPC476439 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	155
0.1-0.2	1081
0.2-0.3	5250
0.3-0.4	15578
0.4-0.5	9530
0.5-0.6	6745
0.6-0.7	3806
0.7-0.8	542
0.8-0.85	6
0.85-0.9	3
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
0.8919	High Similarity	NPC113639
0.88	High Similarity	NPC476317
0.8481	Intermediate Similarity	NPC472471
0.8378	Intermediate Similarity	NPC4299
0.8272	Intermediate Similarity	NPC472473
0.8267	Intermediate Similarity	NPC472254
0.825	Intermediate Similarity	NPC112868
0.8243	Intermediate Similarity	NPC101622
0.8228	Intermediate Similarity	NPC55304
0.8228	Intermediate Similarity	NPC226226
0.8025	Intermediate Similarity	NPC325031
0.8	Intermediate Similarity	NPC471537
0.8	Intermediate Similarity	NPC325869
0.8	Intermediate Similarity	NPC22301
0.7975	Intermediate Similarity	NPC84360
0.7975	Intermediate Similarity	NPC40049
0.7973	Intermediate Similarity	NPC472266
0.7955	Intermediate Similarity	NPC472467
0.7931	Intermediate Similarity	NPC177641
0.7922	Intermediate Similarity	NPC477085
0.7901	Intermediate Similarity	NPC472470
0.7901	Intermediate Similarity	NPC80622
0.7882	Intermediate Similarity	NPC471657
0.7882	Intermediate Similarity	NPC45957
0.7875	Intermediate Similarity	NPC470944
0.7875	Intermediate Similarity	NPC474005
0.7867	Intermediate Similarity	NPC224532
0.7857	Intermediate Similarity	NPC474694
0.7857	Intermediate Similarity	NPC475860
0.7857	Intermediate Similarity	NPC473659
0.7848	Intermediate Similarity	NPC279537
0.7831	Intermediate Similarity	NPC49208
0.7831	Intermediate Similarity	NPC23748
0.7831	Intermediate Similarity	NPC474809
0.7816	Intermediate Similarity	NPC472466
0.7816	Intermediate Similarity	NPC473448
0.7805	Intermediate Similarity	NPC471661
0.7805	Intermediate Similarity	NPC474894
0.7792	Intermediate Similarity	NPC477087
0.7792	Intermediate Similarity	NPC477086
0.7778	Intermediate Similarity	NPC89128
0.7778	Intermediate Similarity	NPC86971
0.7778	Intermediate Similarity	NPC242767
0.7765	Intermediate Similarity	NPC137253
0.7765	Intermediate Similarity	NPC311163
0.7763	Intermediate Similarity	NPC304690
0.7763	Intermediate Similarity	NPC74722
0.7763	Intermediate Similarity	NPC269841
0.775	Intermediate Similarity	NPC186109
0.7738	Intermediate Similarity	NPC474693
0.7727	Intermediate Similarity	NPC472468
0.7722	Intermediate Similarity	NPC215215
0.7722	Intermediate Similarity	NPC329852
0.7722	Intermediate Similarity	NPC265921
0.7722	Intermediate Similarity	NPC85831
0.7654	Intermediate Similarity	NPC260814
0.7654	Intermediate Similarity	NPC267231
0.7654	Intermediate Similarity	NPC27949
0.7654	Intermediate Similarity	NPC39547
0.7654	Intermediate Similarity	NPC323249
0.7647	Intermediate Similarity	NPC471795
0.7625	Intermediate Similarity	NPC472472
0.7625	Intermediate Similarity	NPC310643
0.7625	Intermediate Similarity	NPC469880
0.7625	Intermediate Similarity	NPC271070
0.7625	Intermediate Similarity	NPC301525
0.7619	Intermediate Similarity	NPC477667
0.7619	Intermediate Similarity	NPC231601
0.7619	Intermediate Similarity	NPC250315
0.7619	Intermediate Similarity	NPC311070
0.7614	Intermediate Similarity	NPC209816
0.759	Intermediate Similarity	NPC88735
0.759	Intermediate Similarity	NPC59994
0.759	Intermediate Similarity	NPC78677
0.7568	Intermediate Similarity	NPC300593
0.7568	Intermediate Similarity	NPC309300
0.7564	Intermediate Similarity	NPC471662
0.7564	Intermediate Similarity	NPC477084
0.7558	Intermediate Similarity	NPC477668
0.7558	Intermediate Similarity	NPC116575
0.7532	Intermediate Similarity	NPC265574
0.7532	Intermediate Similarity	NPC329989
0.7532	Intermediate Similarity	NPC239373
0.7529	Intermediate Similarity	NPC37005
0.7529	Intermediate Similarity	NPC471301
0.7529	Intermediate Similarity	NPC154893
0.7529	Intermediate Similarity	NPC16887
0.7529	Intermediate Similarity	NPC82297
0.7529	Intermediate Similarity	NPC53011
0.7528	Intermediate Similarity	NPC234335
0.7528	Intermediate Similarity	NPC249034
0.7527	Intermediate Similarity	NPC290802
0.75	Intermediate Similarity	NPC89555
0.75	Intermediate Similarity	NPC210337
0.75	Intermediate Similarity	NPC473647
0.75	Intermediate Similarity	NPC136813
0.7474	Intermediate Similarity	NPC280566
0.7474	Intermediate Similarity	NPC183570
0.7473	Intermediate Similarity	NPC472469
0.7473	Intermediate Similarity	NPC67584
0.7471	Intermediate Similarity	NPC166857
0.7471	Intermediate Similarity	NPC471796
0.7471	Intermediate Similarity	NPC131329
0.7471	Intermediate Similarity	NPC128644
0.747	Intermediate Similarity	NPC233332
0.747	Intermediate Similarity	NPC474739
0.7467	Intermediate Similarity	NPC19569
0.7442	Intermediate Similarity	NPC274448
0.7442	Intermediate Similarity	NPC471494
0.7442	Intermediate Similarity	NPC11804
0.7442	Intermediate Similarity	NPC474369
0.7442	Intermediate Similarity	NPC287015
0.7442	Intermediate Similarity	NPC255307
0.7442	Intermediate Similarity	NPC146850
0.7442	Intermediate Similarity	NPC471185
0.7442	Intermediate Similarity	NPC261380
0.7436	Intermediate Similarity	NPC64234
0.7436	Intermediate Similarity	NPC37929
0.7436	Intermediate Similarity	NPC473361
0.7436	Intermediate Similarity	NPC329904
0.7416	Intermediate Similarity	NPC301969
0.7416	Intermediate Similarity	NPC37607
0.7412	Intermediate Similarity	NPC472377
0.7412	Intermediate Similarity	NPC30502
0.7412	Intermediate Similarity	NPC44261
0.7407	Intermediate Similarity	NPC152017
0.7403	Intermediate Similarity	NPC167527
0.7403	Intermediate Similarity	NPC276290
0.7397	Intermediate Similarity	NPC323153
0.7396	Intermediate Similarity	NPC272632
0.7391	Intermediate Similarity	NPC88009
0.7391	Intermediate Similarity	NPC213078
0.7386	Intermediate Similarity	NPC260343
0.7381	Intermediate Similarity	NPC52861
0.7381	Intermediate Similarity	NPC470241
0.7381	Intermediate Similarity	NPC47031
0.7381	Intermediate Similarity	NPC316844
0.7381	Intermediate Similarity	NPC475944
0.7381	Intermediate Similarity	NPC315731
0.7375	Intermediate Similarity	NPC471659
0.7375	Intermediate Similarity	NPC474758
0.7375	Intermediate Similarity	NPC470686
0.7375	Intermediate Similarity	NPC474280
0.7363	Intermediate Similarity	NPC201725
0.7363	Intermediate Similarity	NPC198853
0.7363	Intermediate Similarity	NPC323008
0.7363	Intermediate Similarity	NPC281775
0.7363	Intermediate Similarity	NPC470010
0.7363	Intermediate Similarity	NPC477131
0.7363	Intermediate Similarity	NPC470013
0.7363	Intermediate Similarity	NPC262133
0.7356	Intermediate Similarity	NPC305475
0.7356	Intermediate Similarity	NPC475461
0.7356	Intermediate Similarity	NPC329692
0.7356	Intermediate Similarity	NPC474045
0.7356	Intermediate Similarity	NPC261253
0.7349	Intermediate Similarity	NPC139712
0.7349	Intermediate Similarity	NPC201225
0.7349	Intermediate Similarity	NPC477088
0.7349	Intermediate Similarity	NPC469690
0.7349	Intermediate Similarity	NPC469617
0.7349	Intermediate Similarity	NPC476701
0.7342	Intermediate Similarity	NPC471660
0.734	Intermediate Similarity	NPC473510
0.734	Intermediate Similarity	NPC230546
0.734	Intermediate Similarity	NPC227865
0.7333	Intermediate Similarity	NPC34883
0.7333	Intermediate Similarity	NPC140233
0.7333	Intermediate Similarity	NPC287744
0.7333	Intermediate Similarity	NPC133698
0.7326	Intermediate Similarity	NPC222634
0.7326	Intermediate Similarity	NPC78673
0.7326	Intermediate Similarity	NPC191476
0.7326	Intermediate Similarity	NPC186155
0.7326	Intermediate Similarity	NPC476804
0.7326	Intermediate Similarity	NPC471302
0.7326	Intermediate Similarity	NPC165064
0.7326	Intermediate Similarity	NPC114979
0.7326	Intermediate Similarity	NPC102048
0.7326	Intermediate Similarity	NPC156485
0.7326	Intermediate Similarity	NPC160517
0.7326	Intermediate Similarity	NPC470077
0.7326	Intermediate Similarity	NPC474776
0.7326	Intermediate Similarity	NPC295799
0.7324	Intermediate Similarity	NPC96663
0.7317	Intermediate Similarity	NPC107668
0.7317	Intermediate Similarity	NPC7563
0.7317	Intermediate Similarity	NPC476703
0.7317	Intermediate Similarity	NPC116177
0.7317	Intermediate Similarity	NPC320630
0.7317	Intermediate Similarity	NPC474278
0.7317	Intermediate Similarity	NPC262747
0.7317	Intermediate Similarity	NPC315394
0.7312	Intermediate Similarity	NPC477949
0.7312	Intermediate Similarity	NPC161493
0.7312	Intermediate Similarity	NPC107243
0.7312	Intermediate Similarity	NPC202705
0.7308	Intermediate Similarity	NPC232812
0.7308	Intermediate Similarity	NPC151481
0.7303	Intermediate Similarity	NPC310236

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 NPC476439 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	147
0.1-0.2	1590
0.2-0.3	4018
0.3-0.4	2371
0.4-0.5	630
0.5-0.6	279
0.6-0.7	95
0.7-0.8	20
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.8072	Intermediate Similarity	NPD6082	Clinical (unspecified phase)
0.7901	Intermediate Similarity	NPD4822	Approved
0.7901	Intermediate Similarity	NPD4819	Approved
0.7901	Intermediate Similarity	NPD5790	Clinical (unspecified phase)
0.7901	Intermediate Similarity	NPD4820	Approved
0.7901	Intermediate Similarity	NPD4821	Approved
0.7831	Intermediate Similarity	NPD5362	Discontinued
0.7654	Intermediate Similarity	NPD5784	Clinical (unspecified phase)
0.7654	Intermediate Similarity	NPD4268	Approved
0.7654	Intermediate Similarity	NPD4271	Approved
0.7619	Intermediate Similarity	NPD5332	Approved
0.7619	Intermediate Similarity	NPD5331	Approved
0.759	Intermediate Similarity	NPD4790	Discontinued
0.7467	Intermediate Similarity	NPD2685	Clinical (unspecified phase)
0.7412	Intermediate Similarity	NPD7154	Phase 3
0.7303	Intermediate Similarity	NPD6051	Approved
0.7294	Intermediate Similarity	NPD6435	Approved
0.7294	Intermediate Similarity	NPD4270	Approved
0.7294	Intermediate Similarity	NPD4269	Approved
0.7273	Intermediate Similarity	NPD4251	Approved
0.7273	Intermediate Similarity	NPD4250	Approved
0.7222	Intermediate Similarity	NPD5785	Approved
0.7176	Intermediate Similarity	NPD5369	Approved
0.7159	Intermediate Similarity	NPD4249	Approved
0.7159	Intermediate Similarity	NPD5786	Approved
0.7143	Intermediate Similarity	NPD7637	Suspended
0.7126	Intermediate Similarity	NPD7338	Clinical (unspecified phase)
0.7059	Intermediate Similarity	NPD4252	Approved
0.7059	Intermediate Similarity	NPD5368	Approved
0.7045	Intermediate Similarity	NPD5363	Approved
0.7033	Intermediate Similarity	NPD7838	Discovery
0.7011	Intermediate Similarity	NPD6695	Phase 3
0.6979	Remote Similarity	NPD7639	Approved
0.6979	Remote Similarity	NPD7640	Approved
0.6951	Remote Similarity	NPD6924	Approved
0.6951	Remote Similarity	NPD6926	Approved
0.6907	Remote Similarity	NPD5344	Discontinued
0.6882	Remote Similarity	NPD6399	Phase 3
0.6875	Remote Similarity	NPD7638	Approved
0.686	Remote Similarity	NPD6930	Phase 2
0.686	Remote Similarity	NPD6931	Approved
0.686	Remote Similarity	NPD7514	Phase 3
0.6842	Remote Similarity	NPD368	Approved
0.6842	Remote Similarity	NPD4792	Clinical (unspecified phase)
0.6824	Remote Similarity	NPD7322	Clinical (unspecified phase)
0.6804	Remote Similarity	NPD6648	Approved
0.6786	Remote Similarity	NPD6933	Approved
0.6744	Remote Similarity	NPD6929	Approved
0.6742	Remote Similarity	NPD6400	Clinical (unspecified phase)
0.6739	Remote Similarity	NPD1695	Approved
0.6703	Remote Similarity	NPD7524	Approved
0.6703	Remote Similarity	NPD7750	Discontinued
0.6702	Remote Similarity	NPD5778	Approved
0.6702	Remote Similarity	NPD5779	Approved
0.6701	Remote Similarity	NPD8029	Clinical (unspecified phase)
0.6667	Remote Similarity	NPD5325	Clinical (unspecified phase)
0.6667	Remote Similarity	NPD46	Approved
0.6667	Remote Similarity	NPD6698	Approved
0.6667	Remote Similarity	NPD7332	Phase 2
0.6667	Remote Similarity	NPD7525	Registered
0.6667	Remote Similarity	NPD8039	Approved
0.6628	Remote Similarity	NPD7145	Approved
0.6596	Remote Similarity	NPD7983	Approved
0.6591	Remote Similarity	NPD6902	Approved
0.6585	Remote Similarity	NPD7144	Approved
0.6585	Remote Similarity	NPD7143	Approved
0.6571	Remote Similarity	NPD6053	Discontinued
0.6569	Remote Similarity	NPD7899	Clinical (unspecified phase)
0.6562	Remote Similarity	NPD1698	Clinical (unspecified phase)
0.6538	Remote Similarity	NPD6371	Approved
0.6531	Remote Similarity	NPD4225	Approved
0.6517	Remote Similarity	NPD4752	Clinical (unspecified phase)
0.6517	Remote Similarity	NPD5209	Approved
0.6512	Remote Similarity	NPD6925	Approved
0.6512	Remote Similarity	NPD6932	Approved
0.6512	Remote Similarity	NPD5776	Phase 2
0.6506	Remote Similarity	NPD7150	Approved
0.6506	Remote Similarity	NPD7151	Approved
0.6506	Remote Similarity	NPD7152	Approved
0.6494	Remote Similarity	NPD4246	Clinical (unspecified phase)
0.6484	Remote Similarity	NPD6893	Approved
0.6484	Remote Similarity	NPD1694	Approved
0.6481	Remote Similarity	NPD7115	Discovery
0.6477	Remote Similarity	NPD7509	Discontinued
0.6471	Remote Similarity	NPD7339	Approved
0.6471	Remote Similarity	NPD6942	Approved
0.6463	Remote Similarity	NPD6922	Approved
0.6463	Remote Similarity	NPD6923	Approved
0.6429	Remote Similarity	NPD6083	Phase 2
0.6429	Remote Similarity	NPD6084	Phase 2
0.6421	Remote Similarity	NPD7087	Discontinued
0.6413	Remote Similarity	NPD7521	Approved
0.6413	Remote Similarity	NPD7334	Approved
0.6413	Remote Similarity	NPD6684	Approved
0.6413	Remote Similarity	NPD7146	Approved
0.6413	Remote Similarity	NPD5330	Approved
0.6413	Remote Similarity	NPD6409	Approved
0.6392	Remote Similarity	NPD5695	Phase 3
0.6383	Remote Similarity	NPD6101	Approved
0.6383	Remote Similarity	NPD5370	Suspended
0.6383	Remote Similarity	NPD5764	Clinical (unspecified phase)
0.6374	Remote Similarity	NPD4786	Approved
0.6364	Remote Similarity	NPD4195	Approved
0.6353	Remote Similarity	NPD4785	Approved
0.6353	Remote Similarity	NPD4784	Approved
0.6346	Remote Similarity	NPD6899	Approved
0.6346	Remote Similarity	NPD6881	Approved
0.6344	Remote Similarity	NPD4751	Clinical (unspecified phase)
0.6337	Remote Similarity	NPD7632	Discontinued
0.6321	Remote Similarity	NPD8413	Clinical (unspecified phase)
0.6311	Remote Similarity	NPD5739	Approved
0.6311	Remote Similarity	NPD6675	Approved
0.6311	Remote Similarity	NPD6402	Approved
0.6311	Remote Similarity	NPD7128	Approved
0.631	Remote Similarity	NPD4243	Approved
0.6279	Remote Similarity	NPD8264	Approved
0.6277	Remote Similarity	NPD7513	Clinical (unspecified phase)
0.6277	Remote Similarity	NPD6672	Approved
0.6277	Remote Similarity	NPD5737	Approved
0.6277	Remote Similarity	NPD6903	Approved
0.6273	Remote Similarity	NPD7328	Approved
0.6273	Remote Similarity	NPD7327	Approved
0.6267	Remote Similarity	NPD342	Phase 1
0.625	Remote Similarity	NPD4810	Clinical (unspecified phase)
0.625	Remote Similarity	NPD5693	Phase 1
0.625	Remote Similarity	NPD6411	Approved
0.625	Remote Similarity	NPD5697	Approved
0.625	Remote Similarity	NPD8035	Phase 2
0.625	Remote Similarity	NPD5284	Approved
0.625	Remote Similarity	NPD5281	Approved
0.625	Remote Similarity	NPD8034	Phase 2
0.625	Remote Similarity	NPD7503	Approved
0.6237	Remote Similarity	NPD6098	Approved
0.6226	Remote Similarity	NPD7290	Approved
0.6226	Remote Similarity	NPD6883	Approved
0.6226	Remote Similarity	NPD7102	Approved
0.6222	Remote Similarity	NPD6898	Phase 1
0.6216	Remote Similarity	NPD7516	Approved
0.6207	Remote Similarity	NPD3701	Clinical (unspecified phase)
0.62	Remote Similarity	NPD5696	Approved
0.619	Remote Similarity	NPD6011	Approved
0.619	Remote Similarity	NPD7320	Approved
0.619	Remote Similarity	NPD6686	Approved
0.618	Remote Similarity	NPD6683	Phase 2
0.6168	Remote Similarity	NPD6847	Approved
0.6168	Remote Similarity	NPD6617	Approved
0.6168	Remote Similarity	NPD6649	Approved
0.6168	Remote Similarity	NPD6869	Approved
0.6168	Remote Similarity	NPD6650	Approved
0.6168	Remote Similarity	NPD8130	Phase 1
0.6164	Remote Similarity	NPD6927	Phase 3
0.6162	Remote Similarity	NPD7839	Suspended
0.6161	Remote Similarity	NPD8294	Approved
0.6161	Remote Similarity	NPD8377	Approved
0.6154	Remote Similarity	NPD3667	Approved
0.6132	Remote Similarity	NPD6014	Approved
0.6132	Remote Similarity	NPD6012	Approved
0.6132	Remote Similarity	NPD6372	Approved
0.6132	Remote Similarity	NPD6013	Approved
0.6132	Remote Similarity	NPD6373	Approved
0.6129	Remote Similarity	NPD1733	Clinical (unspecified phase)
0.6129	Remote Similarity	NPD7520	Clinical (unspecified phase)
0.6111	Remote Similarity	NPD6882	Approved
0.6111	Remote Similarity	NPD8297	Approved
0.6106	Remote Similarity	NPD8033	Approved
0.6106	Remote Similarity	NPD8296	Approved
0.6106	Remote Similarity	NPD8380	Approved
0.6106	Remote Similarity	NPD8335	Approved
0.6106	Remote Similarity	NPD8379	Approved
0.6106	Remote Similarity	NPD8378	Approved
0.6095	Remote Similarity	NPD6685	Approved
0.6095	Remote Similarity	NPD5701	Approved
0.6082	Remote Similarity	NPD6079	Approved
0.6064	Remote Similarity	NPD5279	Phase 3
0.6049	Remote Similarity	NPD3197	Phase 1
0.6042	Remote Similarity	NPD6080	Approved
0.6042	Remote Similarity	NPD5328	Approved
0.6042	Remote Similarity	NPD6904	Approved
0.6042	Remote Similarity	NPD6673	Approved
0.6022	Remote Similarity	NPD3666	Approved
0.6022	Remote Similarity	NPD5766	Clinical (unspecified phase)
0.6022	Remote Similarity	NPD3665	Phase 1
0.6022	Remote Similarity	NPD3133	Approved
0.602	Remote Similarity	NPD4202	Approved
0.602	Remote Similarity	NPD5781	Clinical (unspecified phase)
0.6019	Remote Similarity	NPD5211	Phase 2
0.6019	Remote Similarity	NPD6401	Clinical (unspecified phase)
0.6	Remote Similarity	NPD4194	Approved
0.6	Remote Similarity	NPD4192	Approved
0.6	Remote Similarity	NPD4193	Approved
0.6	Remote Similarity	NPD4191	Approved
0.5981	Remote Similarity	NPD6413	Approved
0.5979	Remote Similarity	NPD5207	Approved
0.5978	Remote Similarity	NPD4223	Phase 3
0.5978	Remote Similarity	NPD4221	Approved
0.5962	Remote Similarity	NPD6647	Phase 2
0.5962	Remote Similarity	NPD5738	Clinical (unspecified phase)
0.596	Remote Similarity	NPD7748	Approved
0.596	Remote Similarity	NPD5282	Discontinued
0.5957	Remote Similarity	NPD5329	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