NPASS Compound

Structure

NPC473756 OpenBabel07101719402D 28 29 0 0 1 0 0 0 0 0999 V2000 5.0468 0.6636 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.7788 3.6636 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 8.5109 0.6636 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 10.7429 3.5296 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 9.7429 3.5296 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.0468 2.6636 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3147 -0.3364 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 11.1090 1.1636 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1808 2.1636 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.9128 2.1636 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3147 0.6636 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 10.2429 0.6636 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4487 -0.8364 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 7.6449 2.1636 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 8.5109 2.6636 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 11.1090 2.1636 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4781 0.6581 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1808 1.1636 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.7788 2.6636 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 9.3769 1.1636 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5827 -0.3364 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 9.3769 2.1636 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5000 0.8660 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6691 -0.7431 0.0000 C 0 0 3 0 0 0 0 0 0 0 0 0 10.2429 2.6636 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0933 1.7796 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.4612 -1.7213 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 18 1 0 0 0 0 2 19 1 0 0 0 0 3 20 1 0 0 0 0 4 25 1 0 0 0 0 5 25 1 0 0 0 0 6 9 1 0 0 0 0 6 10 1 0 0 0 0 7 11 1 0 0 0 0 7 13 1 0 0 0 0 8 12 1 0 0 0 0 8 16 1 0 0 0 0 9 18 1 0 0 0 0 10 19 2 0 0 0 0 11 18 2 0 0 0 0 12 20 1 0 0 0 0 13 21 1 0 0 0 0 14 15 1 0 0 0 0 14 19 1 0 0 0 0 15 22 1 0 0 0 0 16 25 1 0 0 0 0 17 21 2 0 0 0 0 17 23 1 0 0 0 0 20 22 2 0 0 0 0 21 24 1 0 0 0 0 22 25 1 0 0 0 0 23 26 2 0 0 0 0 23 28 1 0 0 0 0 24 27 1 0 0 0 0 24 28 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	386.28
Volume:	437.032
LogP:	7.02
LogD:	5.287
LogS:	-3.803
# Rotatable Bonds:	9
TPSA:	53.6
# H-Bond Aceptor:	3
# H-Bond Donor:	2
# Rings:	2
# Heavy Atoms:	3

MedChem Properties

QED Drug-Likeness Score:	0.429
Synthetic Accessibility Score:	3.529
Fsp3:	0.6
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected
GSK Rule:	Rejected
BMS Rule:	0
Golden Triangle Rule:	Rejected
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-5.05
MDCK Permeability:	2.228822086181026e-05
Pgp-inhibitor:	0.148
Pgp-substrate:	0.006
Human Intestinal Absorption (HIA):	0.018
20% Bioavailability (F20%):	0.683
30% Bioavailability (F30%):	0.018

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.068
Plasma Protein Binding (PPB):	94.56925964355469%
Volume Distribution (VD):	3.297
Pgp-substrate:	1.0242012739181519%

ADMET: Metabolism

CYP1A2-inhibitor:	0.189
CYP1A2-substrate:	0.382
CYP2C19-inhibitor:	0.234
CYP2C19-substrate:	0.08
CYP2C9-inhibitor:	0.296
CYP2C9-substrate:	0.983
CYP2D6-inhibitor:	0.6
CYP2D6-substrate:	0.884
CYP3A4-inhibitor:	0.126
CYP3A4-substrate:	0.1

ADMET: Excretion

Clearance (CL):	4.554
Half-life (T1/2):	0.313

ADMET: Toxicity

hERG Blockers:	0.002
Human Hepatotoxicity (H-HT):	0.08
Drug-inuced Liver Injury (DILI):	0.008
AMES Toxicity:	0.002
Rat Oral Acute Toxicity:	0.009
Maximum Recommended Daily Dose:	0.262
Skin Sensitization:	0.935
Carcinogencity:	0.033
Eye Corrosion:	0.032
Eye Irritation:	0.768
Respiratory Toxicity:	0.244

Download Data

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

Natural Product: NPC473756

Natural Product ID:	NPC473756
*Common Name:**	Luffariellolide
IUPAC Name:	3-[(3E,7E)-4,8-dimethyl-10-(2,6,6-trimethylcyclohexen-1-yl)deca-3,7-dienyl]-2-hydroxy-2H-furan-5-one
Synonyms:	Luffariellolide
Standard InCHIKey:	JPWPYTMXSXYUPG-QZPYEDBESA-N
Standard InCHI:	InChI=1S/C25H38O3/c1-18(11-7-13-21-17-23(26)28-24(21)27)9-6-10-19(2)14-15-22-20(3)12-8-16-25(22,4)5/h10-11,17,24,27H,6-9,12-16H2,1-5H3/b18-11+,19-10+
SMILES:	C/C(=CCCC1=CC(=O)OC1O)/CC/C=C(/CCC1=C(C)CCCC1(C)C)C
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL451037
PubChem CID:	5387248
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001283] Terpene lactones [CHEMONTID:0001538] Diterpene lactones

*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
NPO32957	Acanthodendrilla sp.	Species	Dictyodendrillidae	Eukaryota	n.a.	n.a.	n.a.	PMID[14510593]
NPO32957	Acanthodendrilla sp.	Species	Dictyodendrillidae	Eukaryota	n.a.	Indonesia	n.a.	PMID[15568767]
NPO32957	Acanthodendrilla sp.	Species	Dictyodendrillidae	Eukaryota	n.a.	n.a.	n.a.	PMID[18257533]
NPO33221	hyrtios communis	Species	Thorectidae	Eukaryota	n.a.	n.a.	n.a.	PMID[23944963]
NPO32957	Acanthodendrilla sp.	Species	Dictyodendrillidae	Eukaryota	n.a.	n.a.	n.a.	PMID[9834155]
NPO33488	laffaariella sp.	Species	n.a.	n.a.	n.a.	Palau	n.a.	Database[Title]

☑ Note for Reference:
In addition to directly collecting NP source organism data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated them from below databases:
☉ UNPD: Universal Natural Products Database [PMID: 23638153].
☉ StreptomeDB: a database of streptomycetes natural products [PMID: 33051671].
☉ TM-MC: a database of medicinal materials and chemical compounds in Northeast Asian traditional medicine [PMID: 26156871].
☉ TCM@Taiwan: a Traditional Chinese Medicine database [PMID: 21253603].
☉ TCMID: a Traditional Chinese Medicine database [PMID: 29106634].
☉ TCMSP: The traditional Chinese medicine systems pharmacology database and analysis platform [PMID: 24735618].
☉ HerDing: a herb recommendation system to treat diseases using genes and chemicals [PMID: 26980517].
☉ MetaboLights: a metabolomics database [PMID: 27010336].
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

NP Quantity Composition/Concentration

Organism ID	NP ID	Organism Material Preparation	Organism Part	NP Quantity (Standard)	NP Quantity (Minimum)	NP Quantity (Maximum)	Quantity Unit	Reference

☑ Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP quantitative records for specific NP domains (e.g., NPS from foods or herbs) from domain-specific databases. These databases include:
☉ DUKE: Dr. Duke's Phytochemical and Ethnobotanical Databases.
☉ PHENOL EXPLORER: is the first comprehensive database on polyphenol content in foods [PMID: 24103452], its homepage can be accessed at here.
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

Biological Activity

Activity Type	# Activity
ED50	1
IC50	4
MIC	1
Others	11

Activity Type	# Activity
Cell Line	3
CELL-LINE	2
Individual Protein	1
Organism	9
Others	1
SINGLE PROTEIN	1

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT1864	Cell Line	L5178Y	Mus musculus	ED50	=	3.3	ug ml-1	PMID[510623]
NPT3172	Individual Protein	Phospholipase A2 group IIA	Homo sapiens	Inhibition	=	98.0	%	PMID[510624]
NPT82	Cell Line	MDA-MB-231	Homo sapiens	IC50	=	4500.0	nM	PMID[510625]
NPT396	Cell Line	T47D	Homo sapiens	IC50	=	5100.0	nM	PMID[510625]
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	IZ	=	7.0	mm	PMID[510623]
NPT79	Organism	Bacillus subtilis	Bacillus subtilis	IZ	=	7.0	mm	PMID[510623]
NPT19	Organism	Escherichia coli	Escherichia coli	IZ	=	7.0	mm	PMID[510623]
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	IZ	=	11.0	mm	PMID[510623]
NPT79	Organism	Bacillus subtilis	Bacillus subtilis	IZ	=	12.0	mm	PMID[510623]
NPT19	Organism	Escherichia coli	Escherichia coli	IZ	=	10.0	mm	PMID[510623]
NPT20	Organism	Candida albicans	Candida albicans	IZ	=	10.0	mm	PMID[510623]
NPT1780	Organism	Davidiella tassiana	Davidiella tassiana	IZ	=	20.0	mm	PMID[510623]
NPT1780	Organism	Davidiella tassiana	Davidiella tassiana	MIC	=	10.4	ug.mL-1	PMID[510623]
NPT24397	SINGLE PROTEIN	Phospholipase A2	Apis mellifera	IC50	=	230.0	nM	PMID[510624]
NPT2	Others	Unspecified		IC50	=	3600.0	nM	PMID[510625]
NPT20972	CELL-LINE	SU.86.86	Homo sapiens	Activity	>	20.0	%	PMID[510626]

☑ 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 NPC473756 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	159
0.1-0.2	1360
0.2-0.3	7358
0.3-0.4	17580
0.4-0.5	8379
0.5-0.6	6092
0.6-0.7	1592
0.7-0.8	143
0.8-0.85	18
0.85-0.9	7
0.9-0.95	8
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
0.9342	High Similarity	NPC323251
0.9342	High Similarity	NPC324170
0.9342	High Similarity	NPC471298
0.9221	High Similarity	NPC471297
0.9167	High Similarity	NPC476489
0.9167	High Similarity	NPC476490
0.9103	High Similarity	NPC126518
0.9103	High Similarity	NPC471301
0.8987	High Similarity	NPC474860
0.8987	High Similarity	NPC471300
0.8987	High Similarity	NPC163606
0.8933	High Similarity	NPC262747
0.8861	High Similarity	NPC471302
0.8816	High Similarity	NPC474816
0.8816	High Similarity	NPC209135
0.875	High Similarity	NPC42586
0.875	High Similarity	NPC473251
0.8608	High Similarity	NPC471296
0.8481	Intermediate Similarity	NPC475944
0.8434	Intermediate Similarity	NPC474629
0.8415	Intermediate Similarity	NPC211892
0.8395	Intermediate Similarity	NPC470800
0.8353	Intermediate Similarity	NPC477122
0.8333	Intermediate Similarity	NPC470734
0.8293	Intermediate Similarity	NPC329630
0.8272	Intermediate Similarity	NPC474809
0.8267	Intermediate Similarity	NPC257618
0.8214	Intermediate Similarity	NPC472809
0.8214	Intermediate Similarity	NPC472810
0.8171	Intermediate Similarity	NPC31086
0.8171	Intermediate Similarity	NPC474865
0.8161	Intermediate Similarity	NPC298973
0.8161	Intermediate Similarity	NPC104925
0.8158	Intermediate Similarity	NPC222244
0.8158	Intermediate Similarity	NPC16349
0.8049	Intermediate Similarity	NPC42476
0.8049	Intermediate Similarity	NPC472440
0.8023	Intermediate Similarity	NPC477782
0.8	Intermediate Similarity	NPC472378
0.7955	Intermediate Similarity	NPC324078
0.7955	Intermediate Similarity	NPC469697
0.7931	Intermediate Similarity	NPC477783
0.7931	Intermediate Similarity	NPC472811
0.7907	Intermediate Similarity	NPC251528
0.7882	Intermediate Similarity	NPC475678
0.7857	Intermediate Similarity	NPC217394
0.7857	Intermediate Similarity	NPC472442
0.7848	Intermediate Similarity	NPC27205
0.7841	Intermediate Similarity	NPC472812
0.7831	Intermediate Similarity	NPC472377
0.7831	Intermediate Similarity	NPC311070
0.7816	Intermediate Similarity	NPC281942
0.7816	Intermediate Similarity	NPC232426
0.7778	Intermediate Similarity	NPC162346
0.7765	Intermediate Similarity	NPC474062
0.7753	Intermediate Similarity	NPC470255
0.7727	Intermediate Similarity	NPC141831
0.7692	Intermediate Similarity	NPC477719
0.7692	Intermediate Similarity	NPC477718
0.7674	Intermediate Similarity	NPC312561
0.7667	Intermediate Similarity	NPC472441
0.7647	Intermediate Similarity	NPC473659
0.7647	Intermediate Similarity	NPC475860
0.7647	Intermediate Similarity	NPC474694
0.764	Intermediate Similarity	NPC242069
0.7582	Intermediate Similarity	NPC470801
0.7568	Intermediate Similarity	NPC226066
0.7561	Intermediate Similarity	NPC471299
0.7561	Intermediate Similarity	NPC242767
0.7529	Intermediate Similarity	NPC474693
0.7528	Intermediate Similarity	NPC329842
0.7527	Intermediate Similarity	NPC477720
0.7527	Intermediate Similarity	NPC477716
0.7527	Intermediate Similarity	NPC324841
0.7527	Intermediate Similarity	NPC477721
0.75	Intermediate Similarity	NPC472266
0.75	Intermediate Similarity	NPC475709
0.7473	Intermediate Similarity	NPC476488
0.7473	Intermediate Similarity	NPC476487
0.747	Intermediate Similarity	NPC10636
0.7447	Intermediate Similarity	NPC477717
0.7444	Intermediate Similarity	NPC166346
0.7444	Intermediate Similarity	NPC469939
0.7442	Intermediate Similarity	NPC30984
0.7442	Intermediate Similarity	NPC106416
0.7442	Intermediate Similarity	NPC471795
0.7442	Intermediate Similarity	NPC86316
0.7439	Intermediate Similarity	NPC471220
0.7436	Intermediate Similarity	NPC4299
0.7416	Intermediate Similarity	NPC78973
0.7412	Intermediate Similarity	NPC477124
0.7412	Intermediate Similarity	NPC469
0.7407	Intermediate Similarity	NPC477202
0.7363	Intermediate Similarity	NPC475572
0.7363	Intermediate Similarity	NPC474554
0.7356	Intermediate Similarity	NPC131813
0.7356	Intermediate Similarity	NPC471219
0.7349	Intermediate Similarity	NPC17550
0.7342	Intermediate Similarity	NPC472254
0.7333	Intermediate Similarity	NPC179517
0.7333	Intermediate Similarity	NPC329698
0.7333	Intermediate Similarity	NPC165904
0.7326	Intermediate Similarity	NPC475706
0.7317	Intermediate Similarity	NPC477203
0.7312	Intermediate Similarity	NPC98112
0.7308	Intermediate Similarity	NPC101622
0.7303	Intermediate Similarity	NPC174342
0.7303	Intermediate Similarity	NPC5509
0.7297	Intermediate Similarity	NPC317025
0.7297	Intermediate Similarity	NPC317177
0.7297	Intermediate Similarity	NPC329416
0.7297	Intermediate Similarity	NPC326645
0.7294	Intermediate Similarity	NPC474439
0.7294	Intermediate Similarity	NPC474028
0.7294	Intermediate Similarity	NPC471218
0.7273	Intermediate Similarity	NPC254886
0.7273	Intermediate Similarity	NPC471796
0.7263	Intermediate Similarity	NPC63249
0.7253	Intermediate Similarity	NPC53555
0.7253	Intermediate Similarity	NPC115021
0.7241	Intermediate Similarity	NPC65661
0.7241	Intermediate Similarity	NPC474424
0.7241	Intermediate Similarity	NPC471494
0.7237	Intermediate Similarity	NPC282760
0.7234	Intermediate Similarity	NPC474440
0.7234	Intermediate Similarity	NPC473154
0.7222	Intermediate Similarity	NPC469403
0.7222	Intermediate Similarity	NPC202886
0.7222	Intermediate Similarity	NPC182136
0.7222	Intermediate Similarity	NPC280149
0.7222	Intermediate Similarity	NPC221111
0.7215	Intermediate Similarity	NPC469660
0.7209	Intermediate Similarity	NPC161045
0.7209	Intermediate Similarity	NPC474193
0.7209	Intermediate Similarity	NPC12283
0.7209	Intermediate Similarity	NPC30502
0.7204	Intermediate Similarity	NPC240673
0.7204	Intermediate Similarity	NPC17578
0.7204	Intermediate Similarity	NPC165632
0.7195	Intermediate Similarity	NPC469880
0.7188	Intermediate Similarity	NPC201191
0.7188	Intermediate Similarity	NPC134077
0.7188	Intermediate Similarity	NPC472815
0.7179	Intermediate Similarity	NPC276290
0.7174	Intermediate Similarity	NPC474555
0.716	Intermediate Similarity	NPC470686
0.7159	Intermediate Similarity	NPC173917
0.7159	Intermediate Similarity	NPC311163
0.7159	Intermediate Similarity	NPC118266
0.7143	Intermediate Similarity	NPC242945
0.7143	Intermediate Similarity	NPC472814
0.7143	Intermediate Similarity	NPC2882
0.7143	Intermediate Similarity	NPC177037
0.7143	Intermediate Similarity	NPC185587
0.7143	Intermediate Similarity	NPC321728
0.7143	Intermediate Similarity	NPC5908
0.7143	Intermediate Similarity	NPC110373
0.7143	Intermediate Similarity	NPC259156
0.7143	Intermediate Similarity	NPC153095
0.7143	Intermediate Similarity	NPC80471
0.7128	Intermediate Similarity	NPC53844
0.7126	Intermediate Similarity	NPC71626
0.7126	Intermediate Similarity	NPC160517
0.7126	Intermediate Similarity	NPC186155
0.7126	Intermediate Similarity	NPC78673
0.7111	Intermediate Similarity	NPC477748
0.7111	Intermediate Similarity	NPC474396
0.7111	Intermediate Similarity	NPC50488
0.7108	Intermediate Similarity	NPC315394
0.7097	Intermediate Similarity	NPC13924
0.7093	Intermediate Similarity	NPC109938
0.7093	Intermediate Similarity	NPC256112
0.7093	Intermediate Similarity	NPC122945
0.7089	Intermediate Similarity	NPC151481
0.7083	Intermediate Similarity	NPC471075
0.7083	Intermediate Similarity	NPC96663
0.7083	Intermediate Similarity	NPC198992
0.7079	Intermediate Similarity	NPC313658
0.7079	Intermediate Similarity	NPC45409
0.7079	Intermediate Similarity	NPC316138
0.7073	Intermediate Similarity	NPC329852
0.7073	Intermediate Similarity	NPC228978
0.7065	Intermediate Similarity	NPC472195
0.7065	Intermediate Similarity	NPC472954
0.7065	Intermediate Similarity	NPC472303
0.7065	Intermediate Similarity	NPC156553
0.7065	Intermediate Similarity	NPC238090
0.7065	Intermediate Similarity	NPC472196
0.7059	Intermediate Similarity	NPC206062
0.7059	Intermediate Similarity	NPC268827
0.7059	Intermediate Similarity	NPC281880
0.7045	Intermediate Similarity	NPC119001
0.7045	Intermediate Similarity	NPC11804
0.7045	Intermediate Similarity	NPC35933
0.7037	Intermediate Similarity	NPC477085
0.7033	Intermediate Similarity	NPC51486
0.7033	Intermediate Similarity	NPC253186
0.7033	Intermediate Similarity	NPC310479
0.7024	Intermediate Similarity	NPC326753
0.7024	Intermediate Similarity	NPC184737

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 NPC473756 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	136
0.1-0.2	1936
0.2-0.3	4408
0.3-0.4	2031
0.4-0.5	437
0.5-0.6	180
0.6-0.7	16
0.7-0.8	5
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
0.9103	High Similarity	NPD6400	Clinical (unspecified phase)
0.7568	Intermediate Similarity	NPD5325	Clinical (unspecified phase)
0.7297	Intermediate Similarity	NPD4191	Approved
0.7297	Intermediate Similarity	NPD4192	Approved
0.7297	Intermediate Similarity	NPD4193	Approved
0.7297	Intermediate Similarity	NPD4194	Approved
0.7073	Intermediate Similarity	NPD8039	Approved
0.7013	Intermediate Similarity	NPD2685	Clinical (unspecified phase)
0.6897	Remote Similarity	NPD4752	Clinical (unspecified phase)
0.6832	Remote Similarity	NPD6686	Approved
0.6633	Remote Similarity	NPD7640	Approved
0.6633	Remote Similarity	NPD7639	Approved
0.6622	Remote Similarity	NPD4219	Approved
0.6531	Remote Similarity	NPD7638	Approved
0.6531	Remote Similarity	NPD4225	Approved
0.6489	Remote Similarity	NPD5785	Approved
0.6437	Remote Similarity	NPD5784	Clinical (unspecified phase)
0.6421	Remote Similarity	NPD7637	Suspended
0.6364	Remote Similarity	NPD8029	Clinical (unspecified phase)
0.6316	Remote Similarity	NPD46	Approved
0.6316	Remote Similarity	NPD6698	Approved
0.6304	Remote Similarity	NPD6082	Clinical (unspecified phase)
0.6279	Remote Similarity	NPD8264	Approved
0.6273	Remote Similarity	NPD7328	Approved
0.6273	Remote Similarity	NPD7327	Approved
0.6264	Remote Similarity	NPD7154	Phase 3
0.6216	Remote Similarity	NPD7516	Approved
0.6211	Remote Similarity	NPD689	Discontinued
0.6211	Remote Similarity	NPD6051	Approved
0.6164	Remote Similarity	NPD6927	Phase 3
0.6161	Remote Similarity	NPD8294	Approved
0.6161	Remote Similarity	NPD8377	Approved
0.6154	Remote Similarity	NPD5209	Approved
0.6146	Remote Similarity	NPD7838	Discovery
0.6129	Remote Similarity	NPD1694	Approved
0.6111	Remote Similarity	NPD5790	Clinical (unspecified phase)
0.6111	Remote Similarity	NPD8259	Clinical (unspecified phase)
0.6106	Remote Similarity	NPD8380	Approved
0.6106	Remote Similarity	NPD8033	Approved
0.6106	Remote Similarity	NPD8296	Approved
0.6106	Remote Similarity	NPD8335	Approved
0.6106	Remote Similarity	NPD7503	Approved
0.6106	Remote Similarity	NPD8379	Approved
0.6106	Remote Similarity	NPD8378	Approved
0.61	Remote Similarity	NPD6083	Phase 2
0.61	Remote Similarity	NPD6084	Phase 2
0.6087	Remote Similarity	NPD5362	Discontinued
0.6078	Remote Similarity	NPD5344	Discontinued
0.6067	Remote Similarity	NPD7322	Clinical (unspecified phase)
0.6064	Remote Similarity	NPD6684	Approved
0.6064	Remote Similarity	NPD7146	Approved
0.6064	Remote Similarity	NPD5330	Approved
0.6064	Remote Similarity	NPD7521	Approved
0.6064	Remote Similarity	NPD6409	Approved
0.6064	Remote Similarity	NPD7334	Approved
0.6053	Remote Similarity	NPD342	Phase 1
0.602	Remote Similarity	NPD5779	Approved
0.602	Remote Similarity	NPD5778	Approved
0.6019	Remote Similarity	NPD7632	Discontinued
0.6	Remote Similarity	NPD368	Approved
0.596	Remote Similarity	NPD7748	Approved
0.5957	Remote Similarity	NPD1696	Phase 3
0.5957	Remote Similarity	NPD5363	Approved
0.5955	Remote Similarity	NPD6925	Approved
0.5955	Remote Similarity	NPD5776	Phase 2
0.5943	Remote Similarity	NPD6412	Phase 2
0.5938	Remote Similarity	NPD6903	Approved
0.5938	Remote Similarity	NPD6672	Approved
0.5938	Remote Similarity	NPD5737	Approved
0.5938	Remote Similarity	NPD7513	Clinical (unspecified phase)
0.5934	Remote Similarity	NPD4819	Approved
0.5934	Remote Similarity	NPD7514	Phase 3
0.5934	Remote Similarity	NPD7332	Phase 2
0.5934	Remote Similarity	NPD4820	Approved
0.5934	Remote Similarity	NPD4821	Approved
0.5934	Remote Similarity	NPD4822	Approved
0.5918	Remote Similarity	NPD6411	Approved
0.5918	Remote Similarity	NPD7515	Phase 2
0.5915	Remote Similarity	NPD4265	Approved
0.5914	Remote Similarity	NPD5331	Approved
0.5914	Remote Similarity	NPD5332	Approved
0.5914	Remote Similarity	NPD6695	Phase 3
0.5904	Remote Similarity	NPD7331	Phase 2
0.59	Remote Similarity	NPD1698	Clinical (unspecified phase)
0.59	Remote Similarity	NPD5695	Phase 3
0.5897	Remote Similarity	NPD7507	Approved
0.5893	Remote Similarity	NPD7115	Discovery
0.5889	Remote Similarity	NPD4271	Approved
0.5889	Remote Similarity	NPD4268	Approved
0.5889	Remote Similarity	NPD7145	Approved
0.5882	Remote Similarity	NPD6923	Approved
0.5882	Remote Similarity	NPD6922	Approved
0.5875	Remote Similarity	NPD4246	Clinical (unspecified phase)
0.587	Remote Similarity	NPD6902	Approved
0.587	Remote Similarity	NPD4790	Discontinued
0.5859	Remote Similarity	NPD6399	Phase 3
0.5851	Remote Similarity	NPD3665	Phase 1
0.5851	Remote Similarity	NPD7338	Clinical (unspecified phase)
0.5851	Remote Similarity	NPD3666	Approved
0.5851	Remote Similarity	NPD3133	Approved
0.5842	Remote Similarity	NPD7839	Suspended
0.5842	Remote Similarity	NPD4792	Clinical (unspecified phase)
0.5825	Remote Similarity	NPD6648	Approved
0.5824	Remote Similarity	NPD6929	Approved
0.5814	Remote Similarity	NPD7144	Approved
0.5814	Remote Similarity	NPD7143	Approved
0.5806	Remote Similarity	NPD4269	Approved
0.5806	Remote Similarity	NPD4270	Approved
0.5795	Remote Similarity	NPD6926	Approved
0.5795	Remote Similarity	NPD6924	Approved
0.5784	Remote Similarity	NPD7902	Approved
0.578	Remote Similarity	NPD6371	Approved
0.5778	Remote Similarity	NPD4756	Discovery
0.5761	Remote Similarity	NPD6930	Phase 2
0.5761	Remote Similarity	NPD6931	Approved
0.5761	Remote Similarity	NPD4252	Approved
0.5758	Remote Similarity	NPD5693	Phase 1
0.575	Remote Similarity	NPD7319	Approved
0.5747	Remote Similarity	NPD7150	Approved
0.5747	Remote Similarity	NPD7151	Approved
0.5747	Remote Similarity	NPD7152	Approved
0.573	Remote Similarity	NPD7339	Approved
0.573	Remote Similarity	NPD6942	Approved
0.5729	Remote Similarity	NPD4623	Approved
0.5729	Remote Similarity	NPD3618	Phase 1
0.5729	Remote Similarity	NPD5786	Approved
0.5729	Remote Similarity	NPD5279	Phase 3
0.5729	Remote Similarity	NPD4519	Discontinued
0.5728	Remote Similarity	NPD5696	Approved
0.5714	Remote Similarity	NPD5764	Clinical (unspecified phase)
0.5714	Remote Similarity	NPD5328	Approved
0.5714	Remote Similarity	NPD6101	Approved
0.5701	Remote Similarity	NPD6402	Approved
0.5701	Remote Similarity	NPD7128	Approved
0.5701	Remote Similarity	NPD6675	Approved
0.5701	Remote Similarity	NPD4211	Phase 1
0.5701	Remote Similarity	NPD5739	Approved
0.5699	Remote Similarity	NPD6898	Phase 1
0.5688	Remote Similarity	NPD4061	Clinical (unspecified phase)
0.5684	Remote Similarity	NPD4786	Approved
0.5676	Remote Similarity	NPD4220	Pre-registration
0.5676	Remote Similarity	NPD6053	Discontinued
0.5676	Remote Similarity	NPD6882	Approved
0.5673	Remote Similarity	NPD6404	Discontinued
0.567	Remote Similarity	NPD7524	Approved
0.567	Remote Similarity	NPD7750	Discontinued
0.567	Remote Similarity	NPD4251	Approved
0.567	Remote Similarity	NPD4250	Approved
0.5667	Remote Similarity	NPD3701	Clinical (unspecified phase)
0.5667	Remote Similarity	NPD6933	Approved
0.5652	Remote Similarity	NPD7645	Phase 2
0.5652	Remote Similarity	NPD4195	Approved
0.5638	Remote Similarity	NPD3667	Approved
0.5638	Remote Similarity	NPD6435	Approved
0.5604	Remote Similarity	NPD6932	Approved
0.56	Remote Similarity	NPD7983	Approved
0.56	Remote Similarity	NPD6079	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