NPASS Compound

Structure

CID236176 OpenBabel06191716032D 21 23 0 0 1 0 0 0 0 0999 V2000 -1.8484 2.4977 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5214 2.9460 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1855 -2.3496 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0981 -2.3660 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0731 1.2729 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3660 0.5658 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3660 -2.3660 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3660 -1.3660 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0000 -0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8143 2.2389 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5000 -2.8660 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6248 -0.4001 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.3660 -2.3660 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.3660 -1.3660 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.5000 -0.8660 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.3660 -1.3660 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.5000 -3.8660 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.8660 -0.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.2321 -2.8660 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 -3.3320 -1.1072 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1 10 1 0 0 0 0 2 10 1 0 0 0 0 4 19 1 0 0 0 0 5 6 1 0 0 0 0 5 10 2 0 0 0 0 6 12 1 0 0 0 0 7 8 1 0 0 0 0 7 11 1 0 0 0 0 8 15 1 0 0 0 0 9 15 1 0 0 0 0 9 20 1 0 0 0 0 11 13 1 0 0 0 0 11 17 2 0 0 0 0 12 14 1 6 0 0 0 12 21 1 0 0 0 0 13 16 1 1 0 0 0 13 19 1 0 0 0 0 14 3 1 6 0 0 0 14 16 1 0 0 0 0 14 21 1 0 0 0 0 15 16 1 6 0 0 0 15 20 1 0 0 0 0 16 18 1 1 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	296.16
Volume:	298.301
LogP:	2.223
LogD:	1.107
LogS:	-3.76
# Rotatable Bonds:	4
TPSA:	71.59
# H-Bond Aceptor:	5
# H-Bond Donor:	1
# Rings:	3
# Heavy Atoms:	5

MedChem Properties

QED Drug-Likeness Score:	0.627
Synthetic Accessibility Score:	5.321
Fsp3:	0.812
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Accepted
GSK Rule:	Accepted
BMS Rule:	1
Golden Triangle Rule:	Accepted
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-4.841
MDCK Permeability:	1.2285859156691004e-05
Pgp-inhibitor:	0.003
Pgp-substrate:	0.885
Human Intestinal Absorption (HIA):	0.018
20% Bioavailability (F20%):	0.029
30% Bioavailability (F30%):	0.065

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.938
Plasma Protein Binding (PPB):	68.1191177368164%
Volume Distribution (VD):	1.079
Pgp-substrate:	29.620738983154297%

ADMET: Metabolism

CYP1A2-inhibitor:	0.011
CYP1A2-substrate:	0.958
CYP2C19-inhibitor:	0.018
CYP2C19-substrate:	0.807
CYP2C9-inhibitor:	0.01
CYP2C9-substrate:	0.02
CYP2D6-inhibitor:	0.004
CYP2D6-substrate:	0.091
CYP3A4-inhibitor:	0.025
CYP3A4-substrate:	0.397

ADMET: Excretion

Clearance (CL):	8.011
Half-life (T1/2):	0.551

ADMET: Toxicity

hERG Blockers:	0.029
Human Hepatotoxicity (H-HT):	0.71
Drug-inuced Liver Injury (DILI):	0.18
AMES Toxicity:	0.434
Rat Oral Acute Toxicity:	0.825
Maximum Recommended Daily Dose:	0.212
Skin Sensitization:	0.486
Carcinogencity:	0.92
Eye Corrosion:	0.008
Eye Irritation:	0.063
Respiratory Toxicity:	0.514

Download Data

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

Natural Product: NPC236176

Natural Product ID:	NPC236176
*Common Name:**	Ovalicin
IUPAC Name:	(3S,4R,5S)-4-hydroxy-5-methoxy-4-[(2S,3R)-2-methyl-3-(3-methylbut-2-enyl)oxiran-2-yl]-1-oxaspiro[2.5]octan-6-one
Synonyms:	Ovalicin
Standard InCHIKey:	NESRXFGQJARQNM-OWYFMNJBSA-N
Standard InCHI:	InChI=1S/C16H24O5/c1-10(2)5-6-12-14(3,21-12)16(18)13(19-4)11(17)7-8-15(16)9-20-15/h5,12-13,18H,6-9H2,1-4H3/t12-,13-,14+,15+,16+/m1/s1
SMILES:	CO[C@@H]1C(=O)CC[C@@]2([C@@]1(O)[C@@]1(C)O[C@@H]1CC=C(C)C)CO2
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL562231
PubChem CID:	10957430
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0004603] Organic oxygen compounds [CHEMONTID:0000323] Organooxygen compounds [CHEMONTID:0000129] Alcohols and polyols [CHEMONTID:0001670] Tertiary alcohols

*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
NPO28230	Stemona japonica	Species	Stemonaceae	Eukaryota	stems and leaves	n.a.	n.a.	PMID[18163592]
NPO10946	Pseudallescheria boydii	Species	Microascaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[20509707]
NPO10946	Pseudallescheria boydii	Species	Microascaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[23964677]
NPO41033.1	Pseudallescheria boydii TW-1024-3	Strain	Microascaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[30978020]
NPO28178	Artemisia tridentata	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO28560	Sarcomelicope glauca	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO28407	Clausena heptaphylla	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO28230	Stemona japonica	Species	Stemonaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO28230	Stemona japonica	Species	Stemonaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO28178	Artemisia tridentata	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO28560	Sarcomelicope glauca	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO28407	Clausena heptaphylla	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO28407	Clausena heptaphylla	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO28230	Stemona japonica	Species	Stemonaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO28230	Stemona japonica	Species	Stemonaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO10946	Pseudallescheria boydii	Species	Microascaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO28350	Hypsizigus marmoreus	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[UNPD]
NPO28407	Clausena heptaphylla	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO23206	Senegalia caffra	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO29474	Bipolaris victoriae	Species	Pleosporaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO28178	Artemisia tridentata	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO28463	Penicillium gilmanii	Species	Aspergillaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO28560	Sarcomelicope glauca	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO27851	Leptothorax muscorum	Species	Formicidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO28108	Stereum princeps	Species	Stereaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO28230	Stemona japonica	Species	Stemonaceae	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
GI50	1
IC50	3

Activity Type	# Activity
Cell Line	2
Individual Protein	1
Others	1

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT762	Cell Line	A-431	Homo sapiens	IC50	=	7500.0	nM	PMID[523139]
NPT5373	Individual Protein	Methionine aminopeptidase 2	Homo sapiens	IC50	=	0.4	nM	PMID[523140]
NPT81	Cell Line	A549	Homo sapiens	GI50	=	4100.0	nM	PMID[523141]
NPT27	Others	Unspecified		IC50	=	10000.0	nM	PMID[523139]

☑ 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 NPC236176 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	233
0.1-0.2	1603
0.2-0.3	5374
0.3-0.4	9504
0.4-0.5	15476
0.5-0.6	7801
0.6-0.7	2451
0.7-0.8	249
0.8-0.85	4
0.85-0.9	1
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
0.8654	High Similarity	NPC477266
0.8646	High Similarity	NPC279722
0.84	Intermediate Similarity	NPC478176
0.8286	Intermediate Similarity	NPC476023
0.8224	Intermediate Similarity	NPC80650
0.8085	Intermediate Similarity	NPC262026
0.7909	Intermediate Similarity	NPC296822
0.7826	Intermediate Similarity	NPC225049
0.7818	Intermediate Similarity	NPC474333
0.7778	Intermediate Similarity	NPC474229
0.7757	Intermediate Similarity	NPC87335
0.7748	Intermediate Similarity	NPC476712
0.7748	Intermediate Similarity	NPC476713
0.7742	Intermediate Similarity	NPC67254
0.7736	Intermediate Similarity	NPC474716
0.7736	Intermediate Similarity	NPC469558
0.7706	Intermediate Similarity	NPC473877
0.7692	Intermediate Similarity	NPC39996
0.7679	Intermediate Similarity	NPC17772
0.7658	Intermediate Similarity	NPC207217
0.7658	Intermediate Similarity	NPC270478
0.7658	Intermediate Similarity	NPC476710
0.7658	Intermediate Similarity	NPC476711
0.7636	Intermediate Similarity	NPC7921
0.7636	Intermediate Similarity	NPC208998
0.7632	Intermediate Similarity	NPC102822
0.7632	Intermediate Similarity	NPC477046
0.7615	Intermediate Similarity	NPC171888
0.7615	Intermediate Similarity	NPC317107
0.7615	Intermediate Similarity	NPC194619
0.7615	Intermediate Similarity	NPC146945
0.76	Intermediate Similarity	NPC61275
0.7596	Intermediate Similarity	NPC112613
0.7589	Intermediate Similarity	NPC122033
0.7589	Intermediate Similarity	NPC477116
0.7589	Intermediate Similarity	NPC27999
0.7589	Intermediate Similarity	NPC470854
0.7589	Intermediate Similarity	NPC58662
0.7589	Intermediate Similarity	NPC474654
0.7589	Intermediate Similarity	NPC97908
0.7589	Intermediate Similarity	NPC287343
0.7576	Intermediate Similarity	NPC65359
0.757	Intermediate Similarity	NPC477513
0.7551	Intermediate Similarity	NPC476706
0.7551	Intermediate Similarity	NPC476707
0.7547	Intermediate Similarity	NPC474741
0.7545	Intermediate Similarity	NPC317687
0.7542	Intermediate Similarity	NPC477712
0.7542	Intermediate Similarity	NPC477713
0.7524	Intermediate Similarity	NPC471148
0.7523	Intermediate Similarity	NPC473594
0.7523	Intermediate Similarity	NPC474586
0.7523	Intermediate Similarity	NPC473975
0.7523	Intermediate Similarity	NPC473843
0.7522	Intermediate Similarity	NPC240509
0.7522	Intermediate Similarity	NPC251310
0.7522	Intermediate Similarity	NPC470776
0.75	Intermediate Similarity	NPC251236
0.75	Intermediate Similarity	NPC469627
0.75	Intermediate Similarity	NPC29827
0.75	Intermediate Similarity	NPC475441
0.75	Intermediate Similarity	NPC473802
0.75	Intermediate Similarity	NPC96312
0.75	Intermediate Similarity	NPC328374
0.75	Intermediate Similarity	NPC230623
0.75	Intermediate Similarity	NPC469551
0.75	Intermediate Similarity	NPC179626
0.75	Intermediate Similarity	NPC40632
0.75	Intermediate Similarity	NPC136114
0.75	Intermediate Similarity	NPC146852
0.7477	Intermediate Similarity	NPC474101
0.7477	Intermediate Similarity	NPC49451
0.7456	Intermediate Similarity	NPC470777
0.7456	Intermediate Similarity	NPC470186
0.7455	Intermediate Similarity	NPC157476
0.7451	Intermediate Similarity	NPC322188
0.7436	Intermediate Similarity	NPC473919
0.7436	Intermediate Similarity	NPC473709
0.7434	Intermediate Similarity	NPC470775
0.7434	Intermediate Similarity	NPC176513
0.7431	Intermediate Similarity	NPC42662
0.7429	Intermediate Similarity	NPC98225
0.7429	Intermediate Similarity	NPC305085
0.7429	Intermediate Similarity	NPC476270
0.7429	Intermediate Similarity	NPC474339
0.7429	Intermediate Similarity	NPC84042
0.7429	Intermediate Similarity	NPC164598
0.7429	Intermediate Similarity	NPC207885
0.7423	Intermediate Similarity	NPC79573
0.7411	Intermediate Similarity	NPC117712
0.7411	Intermediate Similarity	NPC473798
0.7407	Intermediate Similarity	NPC3316
0.7407	Intermediate Similarity	NPC475510
0.7407	Intermediate Similarity	NPC144854
0.7407	Intermediate Similarity	NPC475587
0.7404	Intermediate Similarity	NPC306908
0.74	Intermediate Similarity	NPC477684
0.7387	Intermediate Similarity	NPC474516
0.7387	Intermediate Similarity	NPC471933
0.7379	Intermediate Similarity	NPC260223
0.7379	Intermediate Similarity	NPC8803
0.7379	Intermediate Similarity	NPC94337
0.7379	Intermediate Similarity	NPC477264
0.7374	Intermediate Similarity	NPC163296
0.7373	Intermediate Similarity	NPC217901
0.7373	Intermediate Similarity	NPC471939
0.7368	Intermediate Similarity	NPC204552
0.7368	Intermediate Similarity	NPC297179
0.7368	Intermediate Similarity	NPC188667
0.7364	Intermediate Similarity	NPC100908
0.7358	Intermediate Similarity	NPC283567
0.7358	Intermediate Similarity	NPC474747
0.7353	Intermediate Similarity	NPC258674
0.7345	Intermediate Similarity	NPC477509
0.7345	Intermediate Similarity	NPC474734
0.7339	Intermediate Similarity	NPC154608
0.7339	Intermediate Similarity	NPC192813
0.7339	Intermediate Similarity	NPC322903
0.7339	Intermediate Similarity	NPC473595
0.7339	Intermediate Similarity	NPC94377
0.7339	Intermediate Similarity	NPC277017
0.7339	Intermediate Similarity	NPC473939
0.7339	Intermediate Similarity	NPC117604
0.7339	Intermediate Similarity	NPC293850
0.7328	Intermediate Similarity	NPC472401
0.7327	Intermediate Similarity	NPC476705
0.7321	Intermediate Similarity	NPC477126
0.7321	Intermediate Similarity	NPC33360
0.7321	Intermediate Similarity	NPC198539
0.7315	Intermediate Similarity	NPC470979
0.7315	Intermediate Similarity	NPC470587
0.7315	Intermediate Similarity	NPC16313
0.7315	Intermediate Similarity	NPC470975
0.7315	Intermediate Similarity	NPC103088
0.7315	Intermediate Similarity	NPC9303
0.7311	Intermediate Similarity	NPC471940
0.7311	Intermediate Similarity	NPC475273
0.7311	Intermediate Similarity	NPC168849
0.7308	Intermediate Similarity	NPC20078
0.7308	Intermediate Similarity	NPC111187
0.7308	Intermediate Similarity	NPC190080
0.7308	Intermediate Similarity	NPC134454
0.7308	Intermediate Similarity	NPC473574
0.7308	Intermediate Similarity	NPC17326
0.7308	Intermediate Similarity	NPC471916
0.7297	Intermediate Similarity	NPC471243
0.729	Intermediate Similarity	NPC475945
0.729	Intermediate Similarity	NPC475871
0.729	Intermediate Similarity	NPC118902
0.729	Intermediate Similarity	NPC469980
0.729	Intermediate Similarity	NPC104161
0.7288	Intermediate Similarity	NPC24651
0.7281	Intermediate Similarity	NPC156252
0.7281	Intermediate Similarity	NPC473590
0.7281	Intermediate Similarity	NPC98249
0.7281	Intermediate Similarity	NPC469684
0.7281	Intermediate Similarity	NPC53396
0.7273	Intermediate Similarity	NPC475922
0.7273	Intermediate Similarity	NPC141350
0.7273	Intermediate Similarity	NPC471400
0.7273	Intermediate Similarity	NPC16657
0.7273	Intermediate Similarity	NPC204652
0.7273	Intermediate Similarity	NPC471934
0.7265	Intermediate Similarity	NPC312833
0.7265	Intermediate Similarity	NPC19464
0.7264	Intermediate Similarity	NPC477511
0.7264	Intermediate Similarity	NPC264477
0.7264	Intermediate Similarity	NPC474742
0.7264	Intermediate Similarity	NPC201718
0.7264	Intermediate Similarity	NPC47880
0.7264	Intermediate Similarity	NPC181645
0.7257	Intermediate Similarity	NPC268238
0.7257	Intermediate Similarity	NPC73314
0.7257	Intermediate Similarity	NPC323821
0.7257	Intermediate Similarity	NPC143268
0.7257	Intermediate Similarity	NPC45218
0.7257	Intermediate Similarity	NPC247069
0.7255	Intermediate Similarity	NPC212486
0.725	Intermediate Similarity	NPC476078
0.725	Intermediate Similarity	NPC476091
0.7248	Intermediate Similarity	NPC72813
0.7248	Intermediate Similarity	NPC324327
0.7248	Intermediate Similarity	NPC194620
0.7248	Intermediate Similarity	NPC266514
0.7248	Intermediate Similarity	NPC474421
0.7248	Intermediate Similarity	NPC326994
0.7241	Intermediate Similarity	NPC112038
0.7241	Intermediate Similarity	NPC475003
0.7241	Intermediate Similarity	NPC478051
0.7238	Intermediate Similarity	NPC264378
0.7238	Intermediate Similarity	NPC152480
0.7228	Intermediate Similarity	NPC469464
0.7227	Intermediate Similarity	NPC470973
0.7222	Intermediate Similarity	NPC258532
0.7222	Intermediate Similarity	NPC65523
0.7222	Intermediate Similarity	NPC475036
0.7217	Intermediate Similarity	NPC284707
0.7213	Intermediate Similarity	NPC476193
0.7212	Intermediate Similarity	NPC11396
0.7212	Intermediate Similarity	NPC21302

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 NPC236176 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	206
0.1-0.2	2184
0.2-0.3	3880
0.3-0.4	1912
0.4-0.5	650
0.5-0.6	264
0.6-0.7	51
0.7-0.8	3
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
0.7184	Intermediate Similarity	NPD5282	Discontinued
0.7182	Intermediate Similarity	NPD5345	Clinical (unspecified phase)
0.7103	Intermediate Similarity	NPD5344	Discontinued
0.7059	Intermediate Similarity	NPD3168	Discontinued
0.6949	Remote Similarity	NPD6319	Approved
0.6852	Remote Similarity	NPD6648	Approved
0.6827	Remote Similarity	NPD7983	Approved
0.6814	Remote Similarity	NPD4061	Clinical (unspecified phase)
0.6807	Remote Similarity	NPD6054	Approved
0.6807	Remote Similarity	NPD6059	Approved
0.6777	Remote Similarity	NPD8328	Phase 3
0.6762	Remote Similarity	NPD5779	Approved
0.6762	Remote Similarity	NPD5778	Approved
0.6754	Remote Similarity	NPD4634	Approved
0.6754	Remote Similarity	NPD5955	Clinical (unspecified phase)
0.675	Remote Similarity	NPD6016	Approved
0.675	Remote Similarity	NPD6015	Approved
0.6731	Remote Similarity	NPD6698	Approved
0.6731	Remote Similarity	NPD46	Approved
0.6695	Remote Similarity	NPD8295	Clinical (unspecified phase)
0.6694	Remote Similarity	NPD6370	Approved
0.6694	Remote Similarity	NPD5988	Approved
0.6637	Remote Similarity	NPD7899	Clinical (unspecified phase)
0.6635	Remote Similarity	NPD5764	Clinical (unspecified phase)
0.6635	Remote Similarity	NPD6101	Approved
0.6585	Remote Similarity	NPD7492	Approved
0.6581	Remote Similarity	NPD4632	Approved
0.6577	Remote Similarity	NPD3653	Clinical (unspecified phase)
0.6549	Remote Similarity	NPD5739	Approved
0.6549	Remote Similarity	NPD6008	Approved
0.6549	Remote Similarity	NPD6675	Approved
0.6549	Remote Similarity	NPD6402	Approved
0.6549	Remote Similarity	NPD7128	Approved
0.6535	Remote Similarity	NPD6110	Phase 1
0.6532	Remote Similarity	NPD6616	Approved
0.6522	Remote Similarity	NPD6373	Approved
0.6522	Remote Similarity	NPD6372	Approved
0.6514	Remote Similarity	NPD4755	Approved
0.6509	Remote Similarity	NPD6411	Approved
0.6496	Remote Similarity	NPD8297	Approved
0.6491	Remote Similarity	NPD5954	Clinical (unspecified phase)
0.6491	Remote Similarity	NPD5697	Approved
0.6491	Remote Similarity	NPD5701	Approved
0.6486	Remote Similarity	NPD1700	Approved
0.648	Remote Similarity	NPD7078	Approved
0.648	Remote Similarity	NPD8293	Discontinued
0.6475	Remote Similarity	NPD6921	Approved
0.6466	Remote Similarity	NPD6371	Approved
0.6435	Remote Similarity	NPD6881	Approved
0.6435	Remote Similarity	NPD6899	Approved
0.6435	Remote Similarity	NPD7320	Approved
0.6429	Remote Similarity	NPD7736	Approved
0.6417	Remote Similarity	NPD6009	Approved
0.6417	Remote Similarity	NPD7115	Discovery
0.641	Remote Similarity	NPD6649	Approved
0.641	Remote Similarity	NPD6650	Approved
0.6408	Remote Similarity	NPD1733	Clinical (unspecified phase)
0.6404	Remote Similarity	NPD5357	Phase 1
0.6396	Remote Similarity	NPD4700	Approved
0.6396	Remote Similarity	NPD5285	Approved
0.6396	Remote Similarity	NPD4696	Approved
0.6396	Remote Similarity	NPD5286	Approved
0.6379	Remote Similarity	NPD6014	Approved
0.6379	Remote Similarity	NPD6012	Approved
0.6379	Remote Similarity	NPD6013	Approved
0.6371	Remote Similarity	NPD7604	Phase 2
0.6341	Remote Similarity	NPD5983	Phase 2
0.6325	Remote Similarity	NPD6883	Approved
0.6325	Remote Similarity	NPD7290	Approved
0.6325	Remote Similarity	NPD7102	Approved
0.6306	Remote Similarity	NPD4225	Approved
0.6299	Remote Similarity	NPD6033	Approved
0.6293	Remote Similarity	NPD6011	Approved
0.6286	Remote Similarity	NPD7524	Approved
0.6283	Remote Similarity	NPD5225	Approved
0.6283	Remote Similarity	NPD5226	Approved
0.6283	Remote Similarity	NPD5211	Phase 2
0.6283	Remote Similarity	NPD4633	Approved
0.6283	Remote Similarity	NPD5224	Approved
0.6273	Remote Similarity	NPD4697	Phase 3
0.6271	Remote Similarity	NPD6617	Approved
0.6271	Remote Similarity	NPD6847	Approved
0.6271	Remote Similarity	NPD6869	Approved
0.6271	Remote Similarity	NPD8130	Phase 1
0.6239	Remote Similarity	NPD8132	Clinical (unspecified phase)
0.6228	Remote Similarity	NPD5175	Approved
0.6228	Remote Similarity	NPD5174	Approved
0.6218	Remote Similarity	NPD6882	Approved
0.621	Remote Similarity	NPD8513	Phase 3
0.621	Remote Similarity	NPD8516	Approved
0.621	Remote Similarity	NPD8515	Approved
0.621	Remote Similarity	NPD8517	Approved
0.6207	Remote Similarity	NPD6412	Phase 2
0.6195	Remote Similarity	NPD5223	Approved
0.6182	Remote Similarity	NPD5695	Phase 3
0.6182	Remote Similarity	NPD1698	Clinical (unspecified phase)
0.6176	Remote Similarity	NPD5369	Approved
0.6174	Remote Similarity	NPD5141	Approved
0.6161	Remote Similarity	NPD5696	Approved
0.6147	Remote Similarity	NPD6399	Phase 3
0.6142	Remote Similarity	NPD6336	Discontinued
0.6134	Remote Similarity	NPD8413	Clinical (unspecified phase)
0.6134	Remote Similarity	NPD6401	Clinical (unspecified phase)
0.6126	Remote Similarity	NPD5221	Approved
0.6126	Remote Similarity	NPD5222	Approved
0.6126	Remote Similarity	NPD5220	Clinical (unspecified phase)
0.6124	Remote Similarity	NPD7319	Approved
0.6121	Remote Similarity	NPD4768	Approved
0.6121	Remote Similarity	NPD4767	Approved
0.6117	Remote Similarity	NPD6435	Approved
0.6117	Remote Similarity	NPD4800	Clinical (unspecified phase)
0.6111	Remote Similarity	NPD7838	Discovery
0.6087	Remote Similarity	NPD4754	Approved
0.6078	Remote Similarity	NPD4695	Discontinued
0.6071	Remote Similarity	NPD6084	Phase 2
0.6071	Remote Similarity	NPD6083	Phase 2
0.6071	Remote Similarity	NPD7902	Approved
0.6071	Remote Similarity	NPD5173	Approved
0.6066	Remote Similarity	NPD6274	Approved
0.6064	Remote Similarity	NPD7331	Phase 2
0.6038	Remote Similarity	NPD3618	Phase 1
0.6038	Remote Similarity	NPD5786	Approved
0.6038	Remote Similarity	NPD3574	Clinical (unspecified phase)
0.6019	Remote Similarity	NPD1695	Approved
0.6019	Remote Similarity	NPD5328	Approved
0.6019	Remote Similarity	NPD4753	Phase 2
0.6017	Remote Similarity	NPD5128	Approved
0.6017	Remote Similarity	NPD6686	Approved
0.6017	Remote Similarity	NPD4730	Approved
0.6017	Remote Similarity	NPD4729	Approved
0.6	Remote Similarity	NPD7338	Clinical (unspecified phase)
0.5982	Remote Similarity	NPD7839	Suspended
0.5969	Remote Similarity	NPD8074	Phase 3
0.5962	Remote Similarity	NPD3667	Approved
0.5952	Remote Similarity	NPD8274	Clinical (unspecified phase)
0.5946	Remote Similarity	NPD7748	Approved
0.5922	Remote Similarity	NPD5368	Approved
0.592	Remote Similarity	NPD7100	Approved
0.592	Remote Similarity	NPD7101	Approved
0.5917	Remote Similarity	NPD5251	Approved
0.5917	Remote Similarity	NPD5247	Approved
0.5917	Remote Similarity	NPD5249	Phase 3
0.5917	Remote Similarity	NPD5250	Approved
0.5917	Remote Similarity	NPD5248	Approved
0.5909	Remote Similarity	NPD7637	Suspended
0.5909	Remote Similarity	NPD6079	Approved
0.5906	Remote Similarity	NPD8080	Discontinued
0.5905	Remote Similarity	NPD6695	Phase 3
0.5893	Remote Similarity	NPD4629	Approved
0.5893	Remote Similarity	NPD5210	Approved
0.5891	Remote Similarity	NPD7507	Approved
0.5888	Remote Similarity	NPD5279	Phase 3
0.5887	Remote Similarity	NPD6317	Approved
0.5868	Remote Similarity	NPD5217	Approved
0.5868	Remote Similarity	NPD5216	Approved
0.5868	Remote Similarity	NPD5215	Approved
0.5859	Remote Similarity	NPD7642	Approved
0.5856	Remote Similarity	NPD4202	Approved
0.5852	Remote Similarity	NPD8387	Clinical (unspecified phase)
0.5849	Remote Similarity	NPD4786	Approved
0.5842	Remote Similarity	NPD818	Approved
0.5842	Remote Similarity	NPD819	Approved
0.584	Remote Similarity	NPD6335	Approved
0.584	Remote Similarity	NPD6313	Approved
0.584	Remote Similarity	NPD6314	Approved
0.5833	Remote Similarity	NPD5956	Approved
0.5827	Remote Similarity	NPD6908	Approved
0.5827	Remote Similarity	NPD6909	Approved
0.582	Remote Similarity	NPD6053	Discontinued
0.581	Remote Similarity	NPD4269	Approved
0.581	Remote Similarity	NPD4270	Approved
0.5809	Remote Similarity	NPD7966	Clinical (unspecified phase)
0.5804	Remote Similarity	NPD7900	Approved
0.5804	Remote Similarity	NPD7901	Clinical (unspecified phase)
0.5794	Remote Similarity	NPD4522	Approved
0.5789	Remote Similarity	NPD7341	Phase 2
0.5785	Remote Similarity	NPD5135	Approved
0.5785	Remote Similarity	NPD5134	Clinical (unspecified phase)
0.5785	Remote Similarity	NPD5169	Approved
0.578	Remote Similarity	NPD6672	Approved
0.578	Remote Similarity	NPD5737	Approved
0.5778	Remote Similarity	NPD8415	Approved
0.5769	Remote Similarity	NPD8259	Clinical (unspecified phase)
0.5766	Remote Similarity	NPD7515	Phase 2
0.5741	Remote Similarity	NPD6422	Discontinued
0.5739	Remote Similarity	NPD7638	Approved
0.5738	Remote Similarity	NPD5127	Approved
0.5729	Remote Similarity	NPD3704	Approved
0.5714	Remote Similarity	NPD7641	Discontinued
0.5703	Remote Similarity	NPD6291	Clinical (unspecified phase)
0.5701	Remote Similarity	NPD3668	Phase 3
0.5701	Remote Similarity	NPD4197	Approved
0.5701	Remote Similarity	NPD3133	Approved
0.5701	Remote Similarity	NPD3666	Approved
0.5701	Remote Similarity	NPD3665	Phase 1
0.5692	Remote Similarity	NPD8299	Approved
0.5692	Remote Similarity	NPD8342	Approved
0.5692	Remote Similarity	NPD8341	Approved
0.5692	Remote Similarity	NPD8340	Approved
0.569	Remote Similarity	NPD7640	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