NPASS Compound

Natural Product: NPC469447

Natural Product ID	NPC469447
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	3Alpha-O-Caffeoylolean-12-En-27-Oic Acid
IUPAC Name	(4aR,6aR,6aR,6bR,8aR,10R,12aR,14bR)-10-[(E)-3-(3,4-dihydroxyphenyl)prop-2-enoyl]oxy-2,2,4a,6b,9,9,12a-heptamethyl-1,3,4,5,6,6a,7,8,8a,10,11,12,13,14b-tetradecahydropicene-6a-carboxylic acid
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL1079030
PubChem CID	44254694
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001553] Triterpenoids

The Chemical Classification was calculated by Classyfire, a software for chemical taxonomy calculation. Reference: DOI:10.1186/s13321-016-0174-y.

Chemical Representations

RDKit 3D 99104 0 0 0 0 0 0 0 0999 V2000 5.2547 0.0241 -2.9624 O 0 0 0 0 0 0 0 0 0 0 0 0 5.5507 0.3404 -1.7801 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5240 0.4370 -0.8819 O 0 0 0 0 0 0 0 0 0 0 0 0 3.1662 0.1998 -1.2187 C 0 0 2 0 0 0 0 0 0 0 0 0 2.4306 1.4878 -1.0275 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0365 1.3742 -0.5348 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3864 0.0659 -0.9740 C 0 0 1 0 0 0 0 0 0 0 0 0 1.1598 -1.0156 -0.2845 C 0 0 2 0 0 0 0 0 0 0 0 0 2.6288 -0.9552 -0.4362 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1288 -2.2291 -1.1331 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3361 -0.9636 0.9089 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5404 -2.3357 -0.6644 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8673 -2.4296 -0.1210 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7226 -1.2511 -0.4819 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.9891 0.0660 -0.3530 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.8268 1.2345 -0.6756 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2661 0.9620 -0.6128 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8363 -0.1032 -0.0830 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8682 -1.1054 0.5025 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.6316 -2.3369 0.7892 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6530 -1.9462 1.8676 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.6893 -0.9892 1.3369 C 0 0 2 0 0 0 0 0 0 0 0 0 -5.2562 -0.4260 -0.0116 C 0 0 1 0 0 0 0 0 0 0 0 0 -6.2087 0.5838 -0.5380 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.7023 1.6043 0.4290 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.2350 1.6313 0.5308 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.3301 3.0062 -0.0747 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.1021 1.4590 1.7984 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.0881 0.0605 2.3175 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.9369 -1.8540 1.0971 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3958 -0.5223 1.7880 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8320 0.5858 2.2410 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.4448 -1.1256 2.6062 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.2671 -1.5035 -1.8626 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3824 0.0330 -2.4503 C 0 0 0 0 0 0 0 0 0 0 0 0 6.9659 0.5878 -1.4238 C 0 0 0 0 0 0 0 0 0 0 0 0 7.3178 0.9182 -0.2048 C 0 0 0 0 0 0 0 0 0 0 0 0 8.6825 1.1824 0.2458 C 0 0 0 0 0 0 0 0 0 0 0 0 8.9274 1.5233 1.5663 C 0 0 0 0 0 0 0 0 0 0 0 0 10.2302 1.7610 1.9358 C 0 0 0 0 0 0 0 0 0 0 0 0 11.2825 1.6727 1.0501 C 0 0 0 0 0 0 0 0 0 0 0 0 11.0070 1.3366 -0.2350 C 0 0 0 0 0 0 0 0 0 0 0 0 9.7084 1.0918 -0.6360 C 0 0 0 0 0 0 0 0 0 0 0 0 12.0503 1.2417 -1.1443 O 0 0 0 0 0 0 0 0 0 0 0 0 12.5802 1.9139 1.4360 O 0 0 0 0 0 0 0 0 0 0 0 0 3.1773 -0.0613 -2.2975 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9784 2.1788 -0.3194 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4086 2.0552 -1.9955 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0802 1.3105 0.5919 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4567 2.2556 -0.8469 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9267 -0.8988 0.8181 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1982 -3.0665 -0.4332 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1954 -1.9871 -1.4181 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6072 -2.4241 -2.0674 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0902 -1.8879 1.4884 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4270 -0.9027 0.7872 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9807 -0.1075 1.5369 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5996 -2.5664 -1.7355 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1288 -3.1235 -0.1367 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3193 -3.3428 -0.5941 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8354 -2.6474 0.9633 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7546 0.1242 0.7601 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6199 1.7030 -1.6599 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6231 2.0561 0.0729 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9344 1.7056 -1.0412 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9818 -3.1099 1.2713 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1297 -2.8111 -0.0588 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0789 -1.3922 2.6470 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0848 -2.8337 2.3600 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3924 -1.3300 -0.6930 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7743 1.0171 -1.4757 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.1362 0.0624 -0.9317 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.6044 2.6700 0.6722 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.5941 1.0497 1.3899 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.6247 1.2863 -0.4402 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2963 3.2552 0.1829 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.0319 3.7222 0.3507 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.4887 3.0230 -1.1916 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1482 1.9890 1.8279 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.7825 2.0436 2.4872 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3510 0.0255 3.1715 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.0734 -0.1651 2.8162 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.6799 -2.9283 1.0012 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.4960 -1.5729 0.2101 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.6045 -1.8002 2.0056 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4506 -1.0257 3.6159 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0481 -2.3209 -1.8449 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4680 -1.9331 -2.5349 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7621 -0.6615 -2.3421 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6627 -0.9097 -2.9239 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0332 0.8180 -2.8841 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6379 0.3017 -2.8190 H 0 0 0 0 0 0 0 0 0 0 0 0 7.6970 0.4916 -2.1810 H 0 0 0 0 0 0 0 0 0 0 0 0 6.4803 0.9917 0.5106 H 0 0 0 0 0 0 0 0 0 0 0 0 8.0951 1.5903 2.2541 H 0 0 0 0 0 0 0 0 0 0 0 0 10.4732 2.0307 2.9573 H 0 0 0 0 0 0 0 0 0 0 0 0 9.5708 0.8281 -1.6823 H 0 0 0 0 0 0 0 0 0 0 0 0 12.0840 0.4655 -1.8081 H 0 0 0 0 0 0 0 0 0 0 0 0 13.3277 1.4671 0.9387 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 2 0 2 3 1 0 3 4 1 0 4 5 1 0 5 6 1 0 6 7 1 0 7 8 1 0 8 9 1 0 9 10 1 0 9 11 1 0 8 12 1 0 12 13 1 0 13 14 1 0 14 15 1 0 15 16 1 0 16 17 1 0 17 18 2 0 18 19 1 0 19 20 1 0 20 21 1 0 21 22 1 0 22 23 1 0 23 24 1 0 24 25 1 0 25 26 1 0 25 27 1 0 25 28 1 0 28 29 1 0 22 30 1 6 19 31 1 1 31 32 2 0 31 33 1 0 14 34 1 6 7 35 1 6 2 36 1 0 36 37 2 0 37 38 1 0 38 39 2 0 39 40 1 0 40 41 2 0 41 42 1 0 42 43 2 0 42 44 1 0 41 45 1 0 9 4 1 0 19 14 1 0 29 22 1 0 43 38 1 0 15 7 1 0 23 18 1 0 4 46 1 6 5 47 1 0 5 48 1 0 6 49 1 0 6 50 1 0 8 51 1 1 10 52 1 0 10 53 1 0 10 54 1 0 11 55 1 0 11 56 1 0 11 57 1 0 12 58 1 0 12 59 1 0 13 60 1 0 13 61 1 0 15 62 1 1 16 63 1 0 16 64 1 0 17 65 1 0 20 66 1 0 20 67 1 0 21 68 1 0 21 69 1 0 23 70 1 6 24 71 1 0 24 72 1 0 26 73 1 0 26 74 1 0 26 75 1 0 27 76 1 0 27 77 1 0 27 78 1 0 28 79 1 0 28 80 1 0 29 81 1 0 29 82 1 0 30 83 1 0 30 84 1 0 30 85 1 0 33 86 1 0 34 87 1 0 34 88 1 0 34 89 1 0 35 90 1 0 35 91 1 0 35 92 1 0 36 93 1 0 37 94 1 0 39 95 1 0 40 96 1 0 43 97 1 0 44 98 1 0 45 99 1 0 M END

Standard InCHIKey	LWJORTCWCRJUEH-QHCDZFOOSA-N
Standard InCHI	InChI=1S/C39H54O6/c1-34(2)18-19-36(5)20-21-39(33(43)44)25(26(36)23-34)10-12-30-37(6)16-15-31(35(3,4)29(37)14-17-38(30,39)7)45-32(42)13-9-24-8-11-27(40)28(41)22-24/h8-11,13,22,26,29-31,40-41H,12,14-21,23H2,1-7H3,(H,43,44)/b13-9+/t26-,29-,30+,31+,36+,37-,38+,39+/m0/s1
SMILES	O=C(O[C@@H]1CC[C@]2([C@H](C1(C)C)CC[C@@]1([C@@H]2CC=C2[C@]1(CC[C@@]1([C@H]2CC(C)(C)CC1)C)C(=O)O)C)C)/C=C/c1ccc(c(c1)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	618.39	Volume:	666.047 ? Van der Waals volume.
Dense:	0.928	LogP:	4.403 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.373 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.404 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	5.0	Rigid Bonds:	35.0
TPSA:	104.06 ? Topological Polar Surface Area.	H-Bond Acceptor:	6.0
H-Bond Donor:	3.0	Rings:	6.0
Heavy Atoms:	6.0

MedChem Properties

QED Drug-Likeness Score:	0.135	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.933	Fsp³:	0.692
MCE-18:	165.879 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Rejected	GSK Rule:	Accepted
Golden Triangle Rule:	Accepted	BMS Rule:	0
Chelating Alert:	1	PAINS Alert:	1
Colloidal aggregators:	0.986	Fluc inhibitor:	0.713 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.153 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.036 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.262	Promiscuous compounds:	0.107

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.471	MDCK Permeability:	-5.035
Pgp-inhibitor:	0.775	Pgp-substrate:	0.0
PAMPA:	0.958 ? The experimental data for Peff was logarithmically transformed (logPeff). Molecules with log Peff values below 2.0 were classified as low-permeability (Category 0), while those with log Peff values exceeding 2.5 were classified as high-permeability (Category 1).	Human Intestinal Absorption (HIA):	0.0
20% Bioavailability (F20%):	0.965	30% Bioavailability (F30%):	0.906
50% Bioavailability (F50%):	0.998

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.002	MRP1:	0.767
Plasma Protein Binding (PPB):	97.841%	Volume Distribution (VD):	-0.462
Fu:	1.854% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	0.998	BCRP inhibitor:	0.002
BSEP inhibitor:	0.997

ADMET: Metabolism

CYP1A2-inhibitor:	0.045	CYP1A2-substrate:	0.001
CYP2C19-inhibitor:	0.04	CYP2C19-substrate:	0.034
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.529	CYP3A4-substrate:	0.992
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.995
HLM stability:	0.378 ? Human liver microsomal (HLM) stability. Category 0: stable+ (HLM > 30 min); Category 1: unstable- (HLM ≤ 30 min). The output value is the probability of human liver microsomal instability, where a value closer to 1 indicates a higher likelihood of instability.

ADMET: Excretion

Clearance (CL):

3.133

Half-life (T1/2):

1.251

ADMET: Toxicity

hERG Blockers:	0.045	hERG Blockers (10um):	0.137
Human Hepatotoxicity (H-HT):	0.692	Drug-induced Liver Injury (DILI):	0.906
AMES Toxicity:	0.347	Rat Oral Acute Toxicity:	0.293
Maximum Recommended Daily Dose:	0.562	Skin Sensitization:	0.999
Carcinogencity:	0.829	Eye Corrosion:	0.029
Eye Irritation:	0.728	Respiratory Toxicity:	0.601
Drug-induced Neurotoxicity:	0.013	Ototoxicity:	0.7
Hematotoxicity:	0.206	Drug-induced Nephrotoxicity:	0.801
Genotoxicity:	0.941	RPMI-8226 Immunitoxicity:	0.01
A549 Cytotoxicity:	0.521	Hek293 Cytotoxicity:	0.292
BCF:	1.369 ? Bioconcentration factors are used for considering secondary poisoning potential and assessing risks to human health via the food chain. The unit is -log10[(mg/L)/(1000*MW)].	IGC50:	4.738 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.235 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.719 ? 96 hour fathead minnow LC50. The unit of LC50FM is -log10[(mg/L)/(1000*MW)].

Species Source

Organism ID	Organism Name	Taxonomy Level	Family	SuperKingdom	Isolation Part	Collection Location	Collection Time	Reference
NPO24475	Aceriphyllum rossii	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	PMID[19618898]
NPO24475	Aceriphyllum rossii	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[COCONUT]
NPO24475	Aceriphyllum rossii	n.a.	n.a.	n.a.	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	Organism Name	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
Cell line	1
Non-molecular	1

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT83	Cell line	MCF7	Homo sapiens	IC50	>	150000.0	nM	PubChem BioAssay data set
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	>	150000.0	nM	PMID[19618898]

In vivo activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference

Experimental ADME

Experiment Model	Experiment Tissue	ADME Type	ADME Relation	ADME Value	ADME Unit	Reference

Experimental Toxicity

Quantitative toxicity

Experiment Model	Experiment Organism	Toxicity Type	Toxicity Relation	Toxicity Value	Toxicity Unit	Reference

Common Abbreviations:
LC: Lethal Concentration; LD: Lethal Dose; LT:Lethal Time; NOAEL: No-observed-adverse-effect Level; BMDL: Benchmark Dose Lower Confidence Limit; BMD: Benchmark Dose; BMC:Benchmark Concentration; LOAEL: Lowest Observed Adverse Effect Level; RfD:Reference Dose; RfC:Reference Concentration; MRL: Minimal Risk Level; MEG: Maximum Exposure Guideline; PAC: Protective Action Criteria

Categorical toxicity labels

Hepatotoxicity	Carcinogenicity	Mutagenicity	Cardiotoxicity	Respiratory Toxicity	Eye Irritation	Endocrine Disruption

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 toxicity records from domain-specific databases. These databases include:
☉ ToxValDB: a curated database that compiles quantitative toxicity values for chemicals from diverse public sources to support toxicological research and risk assessment.
☉ TOXRIC: a comprehensive, free-to-access, online database providing toxicological/feature data. The toxicity labels are retrieved from this database. [PMID: 36400569]

Chemically structural similarity

Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes approximately 50,000 NPs with experimentally-derived bioactivity available in NPASS)

Similarity is measured using the Tanimoto coefficient (Tc) , which compares the binary fingerprints of two molecules. Tc is calculated as the intersection divided by the union of '1' bits in the fingerprints, ranging from 0 to 1, with 1 indicating highest similarity.

● The left chart: Distribution of similarity level between NPC469447 and all remaining natural products in the NPASS database.
● The right table: Most similar natural products (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	8779
0.1-0.2	36688
0.2-0.3	3952
0.3-0.4	339
0.4-0.5	67
0.5-0.6	25
0.6-0.7	4
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.6875	Remote Similarity	NPC470590
0.6875	Remote Similarity	NPC285184
0.6186	Remote Similarity	NPC477873
0.6	Remote Similarity	NPC86257
0.5943	Remote Similarity	NPC53520
0.5816	Remote Similarity	NPC8102
0.5816	Remote Similarity	NPC66894
0.5682	Remote Similarity	NPC260149
0.567	Remote Similarity	NPC307205
0.55	Remote Similarity	NPC477874
0.5455	Remote Similarity	NPC155192
0.5429	Remote Similarity	NPC610795
0.5393	Remote Similarity	NPC195715
0.5368	Remote Similarity	NPC473612
0.5349	Remote Similarity	NPC17733
0.5349	Remote Similarity	NPC470629
0.5341	Remote Similarity	NPC60755
0.5341	Remote Similarity	NPC1753
0.5341	Remote Similarity	NPC77099
0.5288	Remote Similarity	NPC172311
0.5281	Remote Similarity	NPC209868
0.5275	Remote Similarity	NPC158347
0.5233	Remote Similarity	NPC251779
0.5149	Remote Similarity	NPC182249
0.5149	Remote Similarity	NPC473591
0.5149	Remote Similarity	NPC248287
0.5149	Remote Similarity	NPC234548
0.5096	Remote Similarity	NPC22676
0.5094	Remote Similarity	NPC132126

Similar Clinical/Approved Drugs

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules.

● The left chart: Distribution of similarity level between NPC469447 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3758
0.1-0.2	5306
0.2-0.3	81
0.3-0.4	4
0.4-0.5	1
0.5-0.6	0
0.6-0.7	0
0.7-0.8	0
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
		NPD

Bioactivity similarity

Similar Natural Products in NPASS

Similarity level is defined by 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